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Purpose: To characterize the types of collaterals in eyes with retinal vein occlusion (RVO) and further investigate their correlations with vessel densities of the superficial (SCP) and the deep capillary plexus (DCP) using optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 25 eyes of 23 patients with RVO. 3 x 3 mm2 OCTA macular scans were used to quantify the parafoveal vessel density (VD) of the SCP and DCP, and to classify the collaterals into one of four types (true superficial, true deep, superficial diving, and foveal collateral). Generalized estimating equation (GEE) regression analysis was performed to identify significant associations between parafoveal VD and collaterals. We further compared parafoveal VD between subgroups classified by the presence of specific collateral types based on the results of a clustering algorithm. Results: 16 of 25 eyes (64%) developed collaterals. Of the 43 collateral vessels analyzed, 12/19 (63%) true superficial collaterals developed in eyes with central RVO, while all 10 superficial diving collaterals (100%) developed in eyes with branch RVO. Located exclusively in the SCP, true superficial collaterals were all arteriovenous (A-V), while diving collaterals were all veno-venular (V-V). We found a significant negative correlation between SCP VD and the total number of collaterals (P < 0.001) for the entire study cohort. Furthermore, BRVO eyes that developed superficial diving collaterals and CRVO eyes that developed true superficial collaterals demonstrated significantly lower SCP VD (P-value = 0.014) and DCP VD (P-value = 0.030), respectively, as compared to the eyes without collaterals in the respective RVO group. Conclusion: Our data shows that decreased capillary perfusion in RVO is associated with the development of collaterals, while the RVO type largely dictates the type of collateral that ultimately develops. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to evaluate the nailfold capillary morphological features in patients with exfoliative glaucoma (XFG) and compare them with those pertaining to primary open-angle glaucoma (POAG), normal controls and subjects with exfoliation syndrome (XFS). The second purpose was to investigate all parameters related to platelet function on the hemogram, including the platelet count (PLT), the mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) in patients with XFG. These parameters were subsequently compared with those belonging to normal controls, POAG and XFS subjects. Methods: This case control study involved 152 consecutive patients that were examined at the Glaucoma Department of Clinic for Eye Diseases, Clinical Centre of Serbia, as the referral center for glaucoma in Serbia, between June 2016 and December 2017. Results: Regarding capillaroscopic characteristics, statistically significant difference was found in capillary diameter and tortuosity between the XFG and POAG group (p = 0.050 and p = 0.035) and the XFG and NC group (p = 0.003 and p = 0.044), as well as in the distribution of capillary loops and avascular zones between the XFG and NC group (p = 0.014 and p = 0.004). The subjects with XFG had lower PLT values compared to POAG patients (p = 0.022). Conclusions: In conclusion, to the best of our knowledge, this study marks the first attempt to evaluate capillary morphology as well as to investigate all parameters related to platelet function on the hemogram, in patients with newly diagnosed XFG. Our findings revealed nailfold capillary morphological vascular changes in XFG patients. The subjects with XFG had lower PLT values and a higher MPV serum parameter compared to normal controls and patients with POAG. Further research in this field should therefore aim to evaluate the consequences of the aforementioned microvascular abnormalities in patients with XFG. [ABSTRACT FROM AUTHOR]

Summary: Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle‐aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima–media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end‐diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle‐aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity. [ABSTRACT FROM AUTHOR]

We describe a set of perivascular interneurons (PINs) with series of fibro-vesicular complexes (FVCs) throughout the gray matter of the adult rabbit and rat brains. PIN–FVCs are ubiquitous throughout the brain vasculature as detected in Golgi-impregnated specimens. Most PINs are small, aspiny cells with short or long (> 1 mm) axons that split and travel along arterial blood vessels. Upon ramification, axons form FVCs around the arising vascular branches; then, paired axons run parallel to the vessel wall until another ramification ensues, and a new FVC is formed. Cytologically, FVCs consist of clusters of perivascular bulbs (PVBs) encircling the precapillary and capillary wall surrounded by end-feet and the extracellular matrix of endothelial cells and pericytes. A PVB contains mitochondria, multivesicular bodies, and granules with a membranous core, similar to Meissner corpuscles and other mechanoreceptors. Some PVBs form asymmetrical, axo-spinous synapses with presumptive adjacent neurons. PINs appear to correspond to the type 1 nNOS-positive neurons whose FVCs co-label with markers of sensory fiber-terminals surrounded by astrocytic end-feet. The PIN is conserved in adult cats and rhesus monkey specimens. The location, ubiquity throughout the vasculature of the mammalian brain, and cytological organization of the PIN–FVCs suggests that it is a sensory receptor intrinsic to the mammalian neurovascular unit that corresponds to an afferent limb of the sensorimotor feed-back mechanism controlling local blood flow. [ABSTRACT FROM AUTHOR]

BACKGROUND: The development of any disturbance in the Circle of Willis (COW) can change the hemodynamics of blood flow and result in damage to the vascular system. Clinical methods such as TCD for diagnosing an aneurysm or growth factors and rupture can measure blood velocity. Several factors influence the accuracy of TCD that can lead to wrong evaluations and affect the treatment planning. OBJECTIVE: In this study, the conformity between CFD and TCD was accomplished for investigating the accuracy of the clinical method (TCD) in different vessels of the Circle of Willis. METHODS: The realistic three-dimensional models have been produced from angiography images. Considering fluid-structure interaction, a domain of the blood flow and vessel wall has been simulated by the ANSYS.CFX software. The velocity in the cerebral arteries has been calculated and compared with the velocity acquired from TCD. RESULTS: According to the findings, there were significant differences between the results obtained from computational fluid dynamics and Doppler test in different vessels of the Circle of Willis. In some areas, differences close to 80 cm/s were also reported. CONCLUSION: According to the results, there are possibilities of errors in carrying out a Doppler test in some arteries and can lead to wrong estimates and ultimately incorrect decisions. [ABSTRACT FROM AUTHOR]

We have succeeded in measuring the blood flow velocity in microvessels noninvasively, using an advanced multipoint laser Doppler velocimeter (M-LDV). We developed the M-LDV using a semiconductor laser with a wavelength of 785 nm and were able to improve the measurement of opaque fluids, including blood. Initially, the calibration of our equipment was checked by measuring the flow velocity of water in the glass tube with an inner diameter of 0.55 mm. These values were equal to that calculated from the indicated values of a flowmeter and succeeded in imaging the flow velocity distribution in the glass tube as two-dimensional images. Finally, we enlarged the optical magnification, and measured microvessels of an experimental mouse’s ear, and succeeded in imaging the blood flow velocity in microvessels as three-dimensional images. Compared with our previous report [T. Andoh et al., Jpn. J. Appl. Phys., Part 1 48, 017002 (2009)], the spatial resolution was improved by more than a factor of 10. [ABSTRACT FROM AUTHOR]

• A novel integrated 1D model of the entire liver circulatory system is proposed. • Dynamic blood flow and pressure, and vessels elasticity are considered in the model. • Using flow signals from in vivo measurements the proposed model is validated. • Hemodynamic signals along the vasculature are obtained with a low computational cost. ▪ Blood flow rate and pressure can be measured in vivo by invasive and non-invasive techniques in the large vessels of the hepatic vasculature, but it is not possible to do so along the entire liver circulatory system. Here, we develop a novel 1D model of the liver circulatory system to obtain the hemodynamic signals from macrocirculation to microcirculation with a very low computational cost. The model considers structurally well-defined elements that constitute the entire hepatic circulatory system, the hemodynamics (the temporal-dependence of the blood flow rate and pressure), and the elasticity of the vessel walls. Using flow rate signals from in vivo measurements as inputs in the model, we obtain pressure signals within their physiological range of values. Furthermore, the model allows to get and analyze the blood flow rate and pressure signals along any vessel of the hepatic vasculature. The impact of the elasticity of the different model components on the inlet pressures is also tested. A 1D model of the entire blood vascular system of the human liver is presented for the first time. The model allows to obtain the hemodynamic signals along the hepatic vasculature at a low computational cost. The amplitude and shape of the flow and pressure signals has hardly been studied in the small liver vessels. In this sense, the proposed model is a useful non-invasive exploration tool of the characteristics of the hemodynamic signals. In contrast to models that partially address the hepatic vasculature or those using an electrical analogy, the model presented here is made entirely of structurally well-defined elements. Future works will allow to directly emulate structural vascular alterations due to hepatic diseases and studying their impact on pressure and blood flow signals at key locations of the vasculature. [ABSTRACT FROM AUTHOR]

Angiography and Doppler methods used for diagnosing vascular diseases give information on the shape of blood vessels and pointwise blood speed but do not provide detailed information on the flow fields inside the blood vessels. In this study, we developed a method for visualizing blood flow by using coherent synchrotron x rays. This method, which does not require the addition of any contrast agent or tracer particles, visualizes the flow pattern of blood by enhancing the diffraction and interference characteristics of the blood cells. This was achieved by optimizing the sample- (blood) to-detector (charge-coupled device camera) distance and the sample thickness. The proposed method was used to extract quantitative velocity field information from blood flowing inside an opaque microchannel by applying a two-frame particle image velocimetry algorithm to enhanced x-ray images of the blood flow. The measured velocity field data showed a flow structure typical of flow in a macrochannel. [ABSTRACT FROM AUTHOR]

Reductions in cerebral oxygen saturation (ScO2) measured by near infra-red spectroscopy have been found during compensated hypovolemia in the lower body negative pressure (LBNP)-model, which may reflect reduced cerebral blood flow. However, ScO2 may also be contaminated from extracranial (scalp) tissues, mainly supplied by the external carotid artery (ECA), and it is possible that a ScO2 reduction during hypovolemia is caused by reduced scalp, and not cerebral, blood flow. The aim of the present study was to explore the associations between blood flow in precerebral arteries and ScO2 during LBNP-induced hypovolemia. Twenty healthy volunteers were exposed to LBNP 20, 40, 60 and 80 mmHg. Blood flow in the internal carotid artery (ICA), ECA and vertebral artery (VA) was measured by Doppler ultrasound. Stroke volume for calculating cardiac output was measured by suprasternal Doppler. Associations of changes within subjects were examined using linear mixed-effects regression models. LBNP reduced cardiac output, ScO2 and ICA and ECA blood flow. Changes in flow in both ICA and ECA were associated with changes in ScO2 and cardiac output. Flow in the VA did not change during LBNP and changes in VA flow were not associated with changes in ScO2 or cardiac output. During experimental compensated hypovolemia in healthy, conscious subjects, a reduced ScO2 may thus reflect a reduction in both cerebral and extracranial blood flow. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries’ lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure. [ABSTRACT FROM AUTHOR]

Cancers exhibit spatially heterogeneous, unique vascular architectures across individual samples, cell-lines and patients. This inherently disorganised collection of leaky blood vessels contribute significantly to suboptimal treatment efficacy. Preclinical tools are urgently required which incorporate the inherent variability and heterogeneity of tumours to optimise and engineer anti-cancer therapies. In this study, we present a novel computational framework which incorporates whole, realistic tumours extracted ex vivo to efficiently simulate vascular blood flow and interstitial fluid transport in silico for validation against in vivo biomedical imaging. Our model couples Poiseuille and Darcy descriptions of vascular and interstitial flow, respectively, and incorporates spatially heterogeneous blood vessel lumen and interstitial permeabilities to generate accurate predictions of tumour fluid dynamics. Our platform enables highly-controlled experiments to be performed which provide insight into how tumour vascular heterogeneity contributes to tumour fluid transport. We detail the application of our framework to an orthotopic murine glioma (GL261) and a human colorectal carcinoma (LS147T), and perform sensitivity analysis to gain an understanding of the key biological mechanisms which determine tumour fluid transport. Finally we mimic vascular normalization by modifying parameters, such as vascular and interstitial permeabilities, and show that incorporating realistic vasculatures is key to modelling the contrasting fluid dynamic response between tumour samples. Contrary to literature, we show that reducing tumour interstitial fluid pressure is not essential to increase interstitial perfusion and that therapies should seek to develop an interstitial fluid pressure gradient. We also hypothesise that stabilising vessel diameters and permeabilities are not key responses following vascular normalization and that therapy may alter interstitial hydraulic conductivity. Consequently, we suggest that normalizing the interstitial microenvironment may provide a more effective means to increase interstitial perfusion within tumours. [ABSTRACT FROM AUTHOR]

Introduction: During the third trimester of development, the human fetus accumulates fat, an important energy reservoir during the early postnatal period. The fetal liver, perfused by the nutrient-rich and well-oxygenated blood coming directly from the placenta, is assumed to play a central role in these processes. Earlier studies have linked fetal liver blood flow with maternal nutritional status and response to the maternal oral glucose tolerance test. Our aim was to explore the effect of a regular maternal meal on fetal liver blood flow at two timepoints during the third trimester, representing the start and towards the end of the fetal fat accretion period. We also sought to explore the influence of prepregancy body mass index on how the maternal meal affects fetal liver blood flow. Methods: Using ultrasound Doppler, we examined 108 healthy women with singleton pregnancies in gestational weeks 30 and 36. At each visit, the first examination was performed with the participant in a fasting state at 08.30 a.m., followed by a standard breakfast meal of approximately 400 kcal. The examination was repeated after 105 minutes. Umbilical vein and ductus venosus blood flow was estimated from diameter and blood flow velocity measurements. Fetal liver flow was calculated as umbilical vein flow minus ductus venosus flow, and change in liver blood flow as flow after minus before the meal. The total group was divided into a normal-weight group (prepregancy body mass index 18.5–25.0 kg/m2; n = 83) and an overweight group (prepregancy body mass index >25.0 kg/m2; n = 21). Four women with prepregancy body mass index <18.5 kg/m2 were excluded from these analyses. Non-parametric statistical hypothesis tests were used for group comparisons. Results: For the total group, we observed a significant increase in median (10th - 90th percentile) liver flow 28.9 (‒67.9–111.6) ml/min (p = 0.002) following the meal in week 36, but not in week 30, ‒2.63 (‒53.2–65.0) ml/min (p = 0.91). This result in turn yielded a statistically significant increase in delta liver flow from weeks 30 to 36 of 26.0 (‒107.1–146.6) ml/min (p = 0.008). The increase in postprandial liver flow was observed only in the normal-weight group in week 36. Accordingly, the delta liver flow values between the two weight groups were significantly different in week 36 (p = 0.006) but not in week 30 (p = 0.155). Among the normal-weight women, the increase in delta liver blood flow from weeks 30 to 36 was 39.3 (‒83.0–156.1) ml/min (p<0.001); in contrast, we observed no statistically significant change in the overweight group (‒44.5 (‒229.0–123.2) ml/min; p = 0.073). As a substitute for liver size, we divided the delta liver flow values by abdominal circumference and found no changes in the statistical significance results within or between the two weight groups. Conclusion: In our healthy study population, we observed a statistically significant difference in liver blood flow after maternal intake of a regular meal. This effect depended on gestational age and maternal prepregancy body mass index, but apparently was independent of liver size, based on abdominal circumference as a proxy measure. [ABSTRACT FROM AUTHOR]

Objective: Zebrafish has been recently considered an ideal vertebrate for studying developmental biology, genetics, particularly for modeling tumorigenesis, angiogenesis, and regeneration in vivo. However, when a zebrafish matures completely, its body loses transparency, thus making conventional optical imaging techniques difficult for imaging internal anatomy and vasculature. Acoustic wave penetration outperforms optical methods, high-frequency (>30 MHz) ultrasound (HFUS) was consequently an alternative imaging modality for adult zebrafish imaging, particularly for echocardiography However, visualizing peripheral vessels in a zebrafish by using conventional HFUS is still difficult. Methods: In the present study, high-frequency micro-Doppler imaging (HFμDI) based on ultrafast ultrasound imaging was proposed for zebrafish dorsal vascular mapping in vivo. HFμDI uses a 40-MHz ultrasound transducer, which is an ultrafast ultrasound imaging technology with the highest frequency available currently. Blood flow signals were extracted using an eigen-based clutter filter with different settings. Experiments were performed on an 8-month-old wild-type AB-line adult zebrafish. Results: Blood vessels, including intersegmental vessels, parachordal vessel, dorsal longitudinal anastomotic vessel, and dorsal aorta, from the dorsal side of the zebrafish were clearly observed in two-dimensional (2-D) and 3-D HFμDI. Conclusion: The maximum image depth of HFμDI and the minimal diameter of vessel can be detected were 4 mm and 36 μm, respectively; they were determined without any use of microbubbles. The maximum flow velocity range was approximately 3–4 mm/s on the dorsal vessels of the adult zebrafish. Significance: Compared with conventional ultrasound Doppler imaging, HFμDI exhibited superior small vessel imaging. [ABSTRACT FROM AUTHOR]

Abstract Vascular pericytes and smooth muscle cells surround many blood vessels of the body. Their primary roles include vessel stabilization and regulation of the blood flow. The high degree of heterogeneity among these cells is dictated by (1) differences in their developmental origin and (2) their location in the vascular bed. Phenotype switching contributes to this heterogeneity especially following in vitro culture. In the absence of distinguishing molecular markers, functional assays that capture their heterogeneity in vitro are needed. Spatiotemporal changes in intracellular Ca2+ levels and contraction in response to vasoconstrictors reflect the differences between vascular pericyte and smooth muscle cell. In order to capture this heterogeneity in vitro, large ensembles of cells need to be analyzed. Here we developed an automated image processing method to measure intracellular Ca2+ and contraction in large cell groups which in combination with a computational approach for integrative analysis allowed vascular pericytes and smooth muscle cells to be distinguished without knowledge of their anatomical origin. Highlights • Microfluidic assay for real-time intracellular Ca2+ release. • Assessment of contraction using individual cell tracking. • Automated image analysis of Ca2+ release and cell contraction. • Kullback-Leibler divergence estimation for quantitative analysis of differences. [ABSTRACT FROM AUTHOR]

Background and purpose: Aging leads to alterations in cerebrovascular function, and these are thought to contribute to cognitive decline/dementia. Disturbances to cerebral blood flow regulation have been reported, but the findings are inconsistent and to date no study has comprehensively tested the collective and independent contribution of these parameters in the same age range. Such lines of enquiry are vital since aging is a heterogeneous and complex process, with cerebrovascular parameters being differentially affected depending on the individual. A multicomponent comprehensive measure of cerebrovascular function, which accounts for such diversity, is needed to differentiate between healthy young and old adults. Methods: We tested the effect of aging on cerebrovascular function by comparing healthy young adults aged 18–30 and older adults aged 60–75, without cognitive impairments. Cerebrovascular blood flow velocity was assessed using transcranial Doppler ultrasound. Parameters included resting middle cerebral artery velocity (MCAv), neurovascular coupling, cerebrovascular reactivity to CO2 (hypercapnia and hypocapnia), and the pressure-flow response during a sit-to-stand procedure. Results: MANOVA revealed that collectively, the parameters discriminated the groups (p < .001). MCAv and pressure-flow responses were lower in the older group (p < .001). While there were no differences in hypercapnic responses (p = .908) and neurovascular coupling (p = .517), hypocapnic responses were elevated in the old (p = .002). Conclusions: Collectively, cerebrovascular parameters can distinguish between healthy young and older adults, with aging leading to reductions in MCAv, and altering cerebrovascular reactivity and pressure-flow responses under hypotensive conditions. [ABSTRACT FROM AUTHOR]

Abstract Present work concerns the pulsatile blood flow of two-fluid model through porous blood vessels under the effect of radially varying viscosity. Blood is modeled as two-phase fluid model consisting a core region by non-Newtonian (Herschel-Bulkley) fluid and a plasma region modeled as Newtonian fluid. No slip condition has been used on wall and pressure gradient is taken as periodic function of time. Up to first order approximate solutions of governing equations are obtained using perturbation approach. A comparative analysis for relative change in flow resistance between our model and previously studied single and two-fluid models without porous layer near wall has also been done. The wall of the blood vessel is composed by a thin Brinkman (porous) layer. The stress jump condition has been imposed on fluid-porous interface. Analytical expressions for the velocity profile, flow rate, wall shear stress and flow resistance have been obtained for different regions and the effect of plasma layer thickness, varying viscosity, yield stress, permeability and viscosity ratio parameter on the flow variables are pictorially discussed. It is perceived that values of flow rate for two-fluid model with porous region near wall is higher in comparison to two-fluid model without porous region near wall. Present study reveals a significant impact of glycocalyx layer on blood flow through blood vessels with a porous layer near wall. Highlights • In the present work, pulsatile nature of blood flow of two-fluid model through porous blood vessels under the effect of radially varying viscosity has been done. • The combined effect of plasma layer thickness (and hence porous layer thickness), varying viscosity parameters, permeability and viscosity ratio parameter on hemodynamical quantities have been pictorially analyzed and compared with constant viscosity model. • The viscosity ratio parameter (and hence porosity of arterial wall) affects the plug core radius (and hence the yield plane location). • Due to presence of porous region near wall, there is slight phase difference in flow rate and flow resistance between two-fluid model with and without porous region near wall which completely agrees with Tiwari and Deo [A. Tiwari, S. Deo, Pulsatile flow in a cylindrical tube with porous walls: Applications to blood flow, Journal of Porous Media 16(4) (2013) 335-340] approach. • The outcome of above work shows a significant impact of the viscosity ratio parameter and permeability arising due to existence of glycocalyx layer near wall on various hemodynamical quantities such as rate of flow and resistance offered against the flow. [ABSTRACT FROM AUTHOR]

Background: Caffeine is reported to be the most widely used pharmacologically active substance. It causes mental stimulation and increases blood pressure. Acute systolic and diastolic blood pressure response to caffeine attenuates in the course of regular caffeine use; tolerance to cardiovascular responses develops in some people. For some hypertension-prone people coffee ingestion may be harmful, and for others it may be beneficial. The aim of our work was to evaluate the effect of caffeine on postocclusive reactive hyperaemia (PORH), a test of microvascular function, and at the same time to monitor the central effects of caffeine on blood pressure and heart rate. Methods: Heart rate, arterial pressure, and cutaneous laser-Doppler (LD) flux were monitored in 32 healthy volunteers (aged 25.2 ± 4.3 years) before and after they ingested 200 mg of caffeine. LD flux was measured on a finger at rest and after the release of an 8-minute occlusion of digital arteries above the place of LD flux measurement. All parameters obtained after the ingestion of caffeine were compared to the values obtained before caffeine and to the values obtained after a placebo. Results: We found slightly increased arterial pressure as well as decreased heart rate and resting LD flux (Dunnett’s test, p<0.05) after the ingestion of caffeine. Caffeine significantly reduced the PORH response (Dunnett’s test, p<0.01). The power of the low-frequency oscillations (0.06–0.15 Hz) of LD flux, representing vascular myogenic activity, increased significantly after the ingestion of caffeine at rest and during the PORH response. A correlation was found between the number of cups of coffee regularly consumed and resting LD flux values (R = 0.492, p = 0.00422), peak LD flux values during PORH (R = 0.458, p = 0.00847), and the PORH area (R = 0.506, p = 0.00313) after caffeine consumption. Conclusions: From the results, we can conclude that caffeine affects cutaneous microvascular function during rest and during a PORH response, and that it increases blood pressure and decreases heart rate. [ABSTRACT FROM AUTHOR]

Background: Hypoxia and low pulmonary arterial (PA) blood flow stimulate the development of systemic-to-pulmonary collateral blood vessels, which can be an adverse factor when performing the Fontan operation. The aim of this study was to use optical coherence tomography (OCT) to elucidate the morphological changes in PA vasculature after creation of a bidirectional cavopulmonary connection (BCPC) in children. Methods: This prospective study evaluated PA wall thickness and development of PA vasa vasorum (VV) in the distal PA of eight patients (BCPC group, 1.3 ± 0.3 years) and 20 age-matched children with normal pulmonary artery hemodynamics and morphology (Control group, 1.4 ± 0.3 years). VV development was defined by the VV area ratio, defined as the VV area divided by the adventitial area in cross-sectional images. Results: There was no significant difference in PA wall thickness between the BCPC and control groups (0.12 ± 0.03 mm vs. 0.12 ± 0.02 mm, respectively). The VV area ratio was significantly greater in the BCPC group than in the Control group (14.5 ± 3.5% vs. 5.3 ± 1.6%, respectively; p<0.0001). Conclusion: OCT is a promising new tool for evaluating PA pathology, including the development of VV in patients after BCPC. [ABSTRACT FROM AUTHOR]

• Highly irregular vascular branching in the kidney supports effective autoregulation. • The number of myoendothelial gap junctions regulate the spread of conduction. • Gap junctions allow the juxtaglomerular apparatus to function as a syncitium. • Angiotensin II regulates the expression of renal and vascular gap junctions. • Gap junctions in the juxtaglomerular apparatus control renin secretion. The renal vasculature has many peculiarities including highly irregular branching. Renal blood flow must sustain adequate perfusion and maintain a high glomerular filtration. Renal autoregulation helps control renal blood flow. The local autoregulatory mechanism, tubuloglomerular feedback, elicits a vasoconstriction that can be found not only in neighboring nephrons but over large areas of the kidney indicating that the renal vasculature supports strong conduction of vascular responses. The basis for conduction is intercellular communication through gap junctions. The endothelium is strongly coupled and serves as a vascular conduction highway leading the signal to the vascular smooth muscle cells through myoendothelial coupling. Extensive intercellular coupling is also found in renin secreting cells where gap junctions seem to tie the cells together to improve control of renin secretion. Lack of coupling leads to dysregulation of renin secretion and hypertension. However, the activity of the renin-angiotensin system also controls gap junction expression in the kidney. Treatment reducing angiotensin II activity, as used in hypertension treatment, can affect expression of renal and vascular gap junction. [ABSTRACT FROM AUTHOR]

Background. Toshiba Medical System has developed a new Doppler technique [Superb Microvascular Imaging (SMI)] that has improved microvascular flow imaging. SMI depicts perinodular and intranodular thyroid microvascular flow in higher detail compared to standard colour Doppler (CD) and power Doppler (PD) imaging. Objective. Assess the nodular microvascular architecture by SMI compared to CD and PD features in a series of thyroid nodules submitted to fine needle aspiration cytology, in order to evaluate the potential of SMI in detecting thyroid cancer. Materials and Methods. From April 2016 to July 2017, 254 patients with thyroid nodules, evaluated as at high risk for malignancy in agreement with AACE/ACE/AME guidelines, were submitted to cytology. All nodules were previously submitted to ultrasound grayscale, CD, PD, and SMI evaluation. Benign and malignant nodules were stratified in accordance to the number of vessels visualised by SMI: score 1 with a maximum of two blood vessels and score 2 with three or more vessels. Results. Score 1 was found in 59.6% of benign nodules and in 17.9% of malignant nodules, whereas score 2 was found in 40.4% and in 82.1%, respectively (sensitivity 81.7%; specificity 60.5%, p<0.001). Variables significantly associated with malignancy in the univariate analysis were gender (OR, 0.18; 95% CI, 0.08-0.37; p<0.001), vascularity (OR, 1.91; 95% CI, 1.65-3.89; p<0.001), and SMI (OR, 6.72; 95% CI, 3.89-11.59; p<0.001); multivariate logistic model confirmed SMI score 2 as an independent risk factor for malignancy (OR, 6.99; 95% CI, 3.46-12.09; p<0.001). Conclusions. This prospective pilot study showed that SMI can depict intranodular flow in higher detail compared to CDI and PDI, thus improving thyroid cancer detection. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) is a known complication of HCM and is a strong predictor of mortality. We aim to investigate the relationship between microvascular dysfunction measured by quantitative PET and PH in HCM patients. Methods: Eighty-nine symptomatic HCM patients were included in the study. Each patient underwent two 20-min 13N-NH3 dynamic PET scans for rest and stress conditions, respectively. A 2-tissue irreversible compartmental model was used to fit the segments time activity curves for estimating segmental and global myocardial blood flow (MBF) and myocardial flow reserve (MFR). Echocardiographic derived PASP was utilized to estimate PH. Results: Patients were categorized into two groups across PASP: PH (PASP > 36 mmHg) and no-PH (PASP ≤ 36 mmHg). patients with PH had larger left atrium, ratio of higher inflow early diastole (E) and atrial contraction (A) waves, E/A, and ratio of inflow and peak early diastolic waves, E/e', significantly reduced global stress MBF (1.85 ± 0.52 vs. 2.13 ± 0.56 ml/min/g; p = 0.024) and MFR (2.21 ± 0.57 vs. 2.62 ± 0.75; p = 0.005), while the MBFs at rest between the two groups were similar. There were significant negative correlations between global stress MBF/MFR and PASP (stress MBF: r = -0.23, p = 0.03; MFR: r = -0.32, p = 0.002); for regional MBF and MFR measurements, the highest linear correlation coefficients were observed in the septal wall (stress MBF: r = -0.27, p = 0.01; MFR: r = -0.31, p = 0.003). Global MFR was identified to be independent predictor for PH in multivariate regression analysis. Conclusion: Echocardiography-derived PASP is negatively correlated with global MFR measured by 13N-NH3 dynamic PET. Global MFR is suggested to be an index of PH in HCM patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to noninvasively measure regional contributions of vasculature in the human body using magnetohydrodynamic voltages (VMHD) obtained from electrocardiogram (ECG) recordings performed inside MRI’s static magnetic field (B0). Integrating the regional VMHD over the Swave-Twave segment of the cardiac cycle (Vsegment) provides a non-invasive method for measuring regional blood volumes, which can be rapidly obtained during MRI without incurring additional cost. Methods: VMHD was extracted from 12-lead ECG traces acquired during gradual introduction into a 3T MRI. Regional contributions were computed utilizing weights based on B0’s strength at specified distances from isocenter. Vsegment mapping was performed in six subjects and validated against MR angiograms (MRA). Results: Fluctuations in Vsegment, which presented as positive trace deflections, were found to be associated with aortic-arch flow in the thoracic cavity, the main branches of the abdominal aorta, and the bifurcation of the common iliac artery. The largest fluctuation corresponded to the location where the aortic arch was approximately orthogonal to B0. The smallest fluctuations corresponded to areas of vasculature that were parallel to B0. Significant correlations (specifically, Spearman’s ranked correlation coefficients of 0.96 and 0.97 for abdominal and thoracic cavities, respectively) were found between the MRA and Vsegment maps (p < 0.001). Conclusions: A novel non-invasive method to extract regional blood volumes from ECGs was developed and shown to be a rapid means to quantify peripheral and abdominal blood volumes. [ABSTRACT FROM AUTHOR]

In healthy arteries, blood flow is regulated by microvascular tone assessed by changes in blood flow volume and vascular resistance to endothelium-dependent and -independent vasodilators. We developed a novel method of using intravascular ultrasound (IVUS) and a Doppler flow wire to measure changes in blood flow volume and vascular resistance of the profunda arterial bed. We assessed the variability over 6 months in measuring microvascular endothelium-dependent dilation to acetylcholine and endothelium-independent dilation to adenosine in 20 subjects who were part of a larger study of Gulf War Illness without obstructive peripheral artery disease. Vasomotor function was assessed by Infusions of control (dextrose), acetylcholine (10-6M), adenosine (50μg), and nitroglycerin (25μg/ml). 400 IVUS and 240 flow velocity images were measured a mean 6 (SD = 2) months apart blind to measurement and infusion stage. The mean (SD) baseline profunda flow was 227 (172) ml/min and vascular resistance 4.6 x 104 (2.4 x 104) dynes-s/cm5. The intraclass correlation coefficients for 6-month variability for vascular function were excellent (range 0.827–0.995). Bland-Altman analyses showed mean differences of less than 2% for microvascular endothelium-dependent function (flow volume and resistance) and less than 1% for macrovascular endothelium-dependent function with acceptable limits of agreement. In 49 subjects assessing concurrent validity of the technique against atherosclerosis risk factors, we observed greater impairment in microvascular endothelium-dependent function per year of age (flow volume = -1.4% (p = 0.018), vascular resistance = 1.5% (p = 0.015)) and current smoking (flow volume = -36.7% (p = .006), vascular resistance = 50.0% (p<0.001)). This novel method of assessing microvascular vasomotor function had acceptable measurement reproducibility and validity. [ABSTRACT FROM AUTHOR]

Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The relationship between mean arterial pressure (MAP) and coronary blood flow is well described. There is autoregulation within a MAP range of 60 to 140 mmHg providing near constant coronary blood flow. Outside these limits flow becomes pressure-dependent. So far, response of myocardial oxygenation to changes in pressure and flow has been more difficult to assess. While established techniques mostly require invasive approaches, Oxygenation-Sensitive (OS) Cardiovascular Magnetic Resonance (CMR) is a technique that can non-invasively assess changes in myocardial tissue oxygenation. The purpose of this study was to follow myocardial oxygenation over a wide range of blood pressure variation within and outside known coronary autoregulatory limits using OS-CMR, and to relate these data to coronary hemodynamics. Methods: Ten anaesthetized swine (German Large White) underwent left-sided thoracotomy and attachment of a perivascular flow probe to the proximal left anterior descending (LAD) coronary artery for continuous measurement of blood flow (QLAD). Thereafter, animals were transferred into a 3T MRI scanner. Mean arterial pressure (MAP) was varied in 10–15 mmHg steps by administering alpha1-receptor agents phenylephrine or urapidil. For each MAP level, OS-CMR images as well as arterial and coronary sinus blood gas samples were obtained simultaneously during brief periods of apnea. Relative changes (Δ) of coronary sinus oxygen saturation (ScsO2), oxygen delivery (DO2) and demand (MVO2), extraction ratio (O2ER) and excess (Ω) from respective reference levels at a MAP of 70 mmHg were determined and were compared to %change in OS-signal intensity (OS-SI) in simultaneously acquired OS-CMR images. Results: QLAD response indicated autoregulation between MAP levels of 52 mmHg (lower limit) and127 mmHg (upper limit). OS-CMR revealed a global myocardial oxygenation deficit occurring below the lower autoregulation limit, with the nadir of OS-SI at -9.0%. With MAP values surpassing 70 mmHg, relative OS-SI increased to a maximum of +10.6%. Consistent with this, ΔScsO2, ΔDO2, ΔMVO2, ΔO2ER and ΔΩ responses indicated increasing mismatch of oxygenation balance outside the autoregulated zone. Changes in global OS-CMR were significantly correlated with all of these parameters (p≤0.02) except with ΔMVO2. Conclusion: OS-CMR offers a novel and non-invasive route to evaluate the effects of blood pressure variations, as well as of cardiovascular drugs and interventions, on global and regional myocardial oxygenation, as demonstrated in a porcine model. OS-CMR identified mismatch of O2 supply and demand below the lower limit of coronary autoregulation. Vasopressor induced acute hypertension did not compromise myocardial oxygenation in healthy hearts despite increased cardiac workload and O2 demand. The clinical usefulness of OS-CMR remains to be established. [ABSTRACT FROM AUTHOR]

Objectives: Forest fires in South Asia lead to widespread haze, where many healthy individuals develop psychosomatic symptoms. We investigated the effects of haze exposure on cerebral hemodynamics and new symptoms. We hypothesised that vasoactive substances present in the haze, would lead to vasodilation of cerebral vasculature, thereby altering cerebral hemodynamics, which in turn may account for new psychosomatic symptoms. Methods: Seventy-four healthy volunteers were recruited, and serial transcranial Doppler (TCD) ultrasonography was performed to record blood flow parameters of bilateral middle cerebral arteries (MCA). The first TCD was performed in an air-conditioned environment. It was repeated outdoors after the participants spent 30-minutes in the haze environment. The prevailing level of pollutant standards index (PSI) was recorded. Appropriate statistical analyses were performed to compare cerebral hemodynamics at baseline and after haze exposure in all participants. Subgroup analyses were then employed to compare the findings between symptomatic and asymptomatic participants. Results: Study participants’ median age was 30 years (IQR 26–34), and new psychosomatic symptoms were reported by 35 (47.3%). There was a modest but significant decrease in pulsatility index (PI) and resistivity index (RI) in the left MCA after haze exposure (PI: p = 0.026; RI: p = 0.021). When compared to baseline parameters, haze exposure resulted in significantly lower mean PI (p = 0.001) and RI (p = 0.001) in symptomatic patients, but this difference was not present in asymptomatic patients (PI: p = 0.919; RI: p = 0.970). Conclusion: Haze causes significant alterations in cerebral hemodynamics in susceptible individuals, probably responsible for various psychosomatic symptoms. The prognostic implications and health effects of haze require evaluation in a larger study. [ABSTRACT FROM AUTHOR]

Highlights • GLP-1R expression remains an area of active debate in vascular smooth muscle cells and endothelial cells. • GLP-1R agonists have antihypertensive and antiatherosclerotic properties in preclinical and clinical studies. • Whether these actions on the vasculature are directly or indirectly mediated via GLP-1R agonists remains enigmatic. • Vascular actions may partly explain how GLP-1R agonists improve cardiovascular outcomes in people with type 2 diabetes. Abstract Glucagon-like peptide-1 receptor (GLP-1R) agonists augment insulin secretion and are thus used clinically to improve glycemia in subjects with type 2 diabetes (T2D). As recent data reveal marked improvements in cardiovascular outcomes in T2D subjects treated with the GLP-1R agonists liraglutide and semaglutide in the LEADER and SUSTAIN-6 clinical trials respectively, there is growing interest in delineating the mechanism(s) of action for GLP-1R agonist-induced cardioprotection. Of importance, negligible GLP-1R expression in ventricular cardiac myocytes suggests that cardiac-independent actions of GLP-1R agonists may account for the reduced death rates from cardiovascular causes in T2D subjects enrolled in the LEADER trial. Conversely, vascular smooth muscle cells (VSMCs) appear to express the canonical GLP-1R, and GLP-1/GLP-1R agonists exhibit a number of salutary actions on the vascular endothelium that could potentially contribute to GLP-1R agonists directly improving cardiovascular outcomes in subjects with T2D. We review herein the described actions of GLP-1/GLP-1R agonists on the vascular endothelium, which include antiproliferative actions on VSMCs and endothelial cells, reductions in oxidative stress, and increases in nitric oxide generation. GLP-1 also increases microvascular recruitment and microvascular blood flow. Taken together, such actions may explain the antihypertensive and/or antiatherosclerotic actions attributed to GLP-1/GLP-1R agonists in preclinical and clinical studies. Nonetheless, further mechanistic studies are still necessary to determine the relative importance of such actions in accounting for reductions in macrovascular cardiovascular disease in human subjects with T2D treated with GLP-1R agonists. [ABSTRACT FROM AUTHOR]

Introduction: Middle cerebral artery (MCA) and umbilical artery (UA) Doppler blood flow pulsatility indices (PIs) and MCA peak systolic velocity (PSV) are essential variables for clinically evaluating fetal well-being. Here we examined how a maternal meal influenced these Doppler blood flow velocity variables. Methods: This prospective cohort study included 89 healthy Caucasian women with normal singleton pregnancies (median age, 32 years). Measurements were performed at gestational weeks 30 and 36, representing the start and near the end of the energy-depositing period. Measured variables included the MCA-PI, UA-PI, fetal heart rate (FHR) and MCA-PSV. The cerebroplacental ratio (CPR) was calculated as the ratio of MCA-PI to UA-PI. The first examination was performed in the fasting state at 08:30 a.m. Then participants ate a standard breakfast (approximate caloric intake, 400kcal), and the examination was repeated ~105 min after the meal. Results: Without adjustment for FHR, fetal MCA-PI decreased after the meal at week 30 (‒0.115; p = 0.012) and week 36 (‒0.255; p < 0.001). All PI values were negatively correlated with FHR. After adjustment for FHR, MCA-PI still decreased after the meal at week 30 (‒0.087; p = 0.044) and week 36 (‒0.194; p < 0.001). The difference between the two gestational weeks was non-significant (p = 0.075). UA-PI values did not significantly change at week 30 (p = 0.253) or week 36 (p = 0.920). CPR revealed significant postprandial decreases of −0.17 at week 30 (p = 0.006) and −0.22 at week 36 (p = 0.001). Compared to fasting values, MCA-PSV was significantly higher after food intake: +3.9 cm/s at week 30 (p < 0.001) and +5.9 cm/s at week 36 (p < 0.001). Conclusion: In gestational weeks 30 and 36, we observed a postprandial influence that was apparently specific to fetal cerebral blood flow. [ABSTRACT FROM AUTHOR]

Key points: Intrauterine growth restriction (IUGR) increases offspring risk of chronic diseases later in life, including cardiovascular dysfunction.Our prior studies suggest biventricular cardiac dysfunction and vascular impairment in baboons who were IUGR at birth because of moderate maternal nutrient reduction.The current study reveals changes in artery sizes, distensibility, and blood flow pattern in young adult IUGR baboons, which may contribute to cardiac stress.The pattern of abnormality observed suggests that vascular redistribution seen with IUGR in fetal life may continue into adulthood. Maternal nutrient reduction induces intrauterine growth restriction (IUGR), increasing risks of chronic diseases later in life, including cardiovascular dysfunction. Using ultrasound, we determined regional blood flow, blood vessel sizes, and distensibility in IUGR baboons (8 males, 8 females, 8.8 years, similar to 35 human years) and controls (12 males, 12 females, 9.5 years). The measured blood vessels were larger in size in the males compared to females before but not after normalization to body surface area. Smaller IUGR normalized blood vessel sizes were observed in the femoral and external iliac arteries but not the brachial or common carotid arteries and not correlated significantly with birth weight. Mild decrease in distensibility in the IUGR group was seen in the iliac but not the carotid arteries without between‐sex differences. In IUGR baboons there was increased carotid arterial blood flow velocity during late systole and diastole. Overall, our findings support the conclusion that region specific vascular and haemodynamic changes occur with IUGR, which may contribute to the occurrence of later life cardiac dysfunction. The pattern of alteration observed suggests vascular redistribution efforts in response to challenges in the perinatal period may persist into adulthood. Further studies are needed to determine the life course progression of these changes. Key points: Intrauterine growth restriction (IUGR) increases offspring risk of chronic diseases later in life, including cardiovascular dysfunction.Our prior studies suggest biventricular cardiac dysfunction and vascular impairment in baboons who were IUGR at birth because of moderate maternal nutrient reduction.The current study reveals changes in artery sizes, distensibility, and blood flow pattern in young adult IUGR baboons, which may contribute to cardiac stress.The pattern of abnormality observed suggests that vascular redistribution seen with IUGR in fetal life may continue into adulthood. [ABSTRACT FROM AUTHOR]

Abstract The objective of this study was to evaluate the effectiveness of optical Doppler tomography (ODT) using a portable handheld-type probe for investigating the blood flow in blood vessels of cell carcinoma-affected small animal models. To perform in vivo and real-time investigation, we developed a spectral domain-optical Doppler tomography (SD-ODT) system equipped with a portable handheld-type scanning probe, which uses the Kasai autocorrelation algorithm for Doppler imaging. The system capabilities were evaluated by conducting preliminary experiments on flow measurement in a microtube. The study was performed on healthy and squamous cell carcinoma-affected mouse specimens. The results demonstrate the possibilities and advantages of employing an SD-ODT system with handheld-type scanning probe for cell carcinoma investigation in small animal models. [ABSTRACT FROM AUTHOR]

Graphical abstract The action of mechanical forces on blood vessels has been for long time uniquely associated to the effects elicited by the blood flow sensed at the free surface of endothelial cells paving the lumen. Indeed, 'physiologic' (laminar) shear stress has a generalized vasoprotective role via, e.g., release of nitric oxide by endothelial cells (ECs) or factors (e.g. prostacyclin, PDGF-BB and TGF-β1) that keep under control the vascular tone and maintain a quiescent smooth muscle cells (SMCs) phenotype. By contrast, transition from laminar to turbulent (oscillatory) shear stress disturbs vascular homeostasis, and leads to changes in vascular tone, permeability and, ultimately to atherosclerotic plaque development or neointima accumulation. Mechanosensation in blood vessels is not, however, limited anymore to perception of the flow by endothelial cells. In fact, other vascular districts such as the media in arteries and veins are able to sense the tissue mechanics through the ability of SMCs to respond to elongation and compression forces propagated in the vascular wall through the extracellular matrix. Given that variations in physical characteristics of the surrounding extracellular matrix (ECM) can lead SMCs to reversibly transit from quiescent (contractile) to secretory phenotypes and EC cells are subject to direct flow-controlled transcriptional control, the maladaptive remodeling of blood vessels is likely the result from the sum of different forces acting all in concert. In the present contribution, we will attempt at introducing the emerging concept of cell-based mechanosensation into vessel biology as the outcome of combined mechanical triggers acting in the vascular wall. In particular, we will discuss some of the pathways that translate mechanical forces into molecular signals in ECs, SMCs and vascular progenitors, and how these pathways control vascular patterning, homeostasis and, ultimately, disease. Unlabelled Image [ABSTRACT FROM AUTHOR]

A fluid-structure interaction (FSI) model of a left anterior descending (LAD) coronary artery was developed, incorporating transient blood flow, cyclic bending motion of the artery, and myocardial contraction. The three-dimensional (3D) geometry was constructed based on a patient's computed tomography angiography (CTA) data. To simulate disease conditions, a plaque was placed within the LAD to create a 70% stenosis. The bending motion of the blood vessel was prescribed based on the LAD spatial information. The pressure induced by myocardial contraction was applied to the outside of the blood vessel wall. The fluid domain was solved using the Navier-Stokes equations. The arterial wall was defined as a nonlinear elastic, anisotropic, and incompressible material, and the mechanical behavior was described using the modified hyper-elastic Mooney-Rivlin model. The fluid (blood) and solid (vascular wall) domains were fully coupled. The simulation results demonstrated that besides vessel bending/stretching motion, myocardial contraction had a significant effect on local hemodynamics and vascular wall stress/strain distribution. It not only transiently increased blood flow velocity and fluid wall shear stress, but also changed shear stress patterns. The presence of the plaque significantly reduced vascular wall tensile strain. Compared to the coronary artery models developed previously, the current model had improved physiological relevance. [ABSTRACT FROM AUTHOR]

Purpose: The coupling between neural activity and blood flow is a physiological key principle of ocular blood flow regulation. The current study was performed to investigate whether Laser speckle flowgraphy (LSFG), a commercially available technique for measuring blood flow, is capable to assess flicker-induced haemodynamic changes in the retinal and optic nerve head (ONH) circulation. Methods: Twenty healthy subjects were included in this cross sectional study. A commercial LSFG instrument was used to measure blood flow at the ONH as well as in retinal vessels before and during stimulation with flickering light. Mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for the ONH and relative flow volume (RFV) a measure of relative blood flow of the respective retinal vessels. Results: Stimulation with flicker light increased ONH MBR by +17.5%±6.6% (p<0.01). In retinal arteries, flicker stimulation led an increase of +23.8±10.0% (p<0.05) in total RFV. For retinal veins, an increase of +23.1%±11.0 (p<0.05) in total RFV was observed during stimulation. A higher response was observed in nasal RFV compared to temporal RFV in retinal arteries (nasal: +28.9%±20.0%; temporal: +20.4%±17.6%, p<0.05) and veins (nasal: +28.3%±19.6%; temporal +17.8%±18.9%, p<0.05). Conclusion: As shown previously with other techniques, flicker stimulation leads to an increase in retinal and optic nerve head blood flow. Our results indicate that LSFG is an appropriate method for the quantification of retinal and ONH blood flow during visual stimulation and may be used as a non-invasive, easy to use tool to assess neuro-vascular coupling in humans. [ABSTRACT FROM AUTHOR]

Participation in magnetic resonance imaging (MRI) scanning is associated with increased anxiety, thus possibly impacting baseline recording for functional MRI studies. The goal of the paper is to elucidate the significant hemispheric asymmetry between blood-oxygenation-level-dependent (BOLD) signals from precentral gyrus (PCG) and insula in 23 healthy individuals without any former MRI experience recently published in a PLOSONE paper. In addition to BOLD signals state anxiety and heart rate variability (HRV) were analyzed in two resting state sessions (R1, R2). Phase-locking and time delays from BOLD signals were computed in the frequency band 0.07–0.13 Hz. Positive (pTD) and negative time delays (nTD) were found. The pTD characterize descending neural BOLD oscillations spreading from PCG to insula and nTD characterize ascending vascular BOLD oscillations related to blood flow in the middle cerebral artery. HRV power in two low frequency bands 0.06–0.1 Hz and 0.1–0.14 Hz was computed. Based on the anxiety change from R1 to R2, two groups were separated: one with a strong anxiety decline (large change group) and one with a moderate decline or even anxiety increase (small change group). A significant correlation was found only between the left-hemispheric time delay (pTD, nTD) and anxiety change, with a dominance of nTD in the large change group. The analysis of within-scanner HRV revealed a pronounced increase of low frequency power between both resting states, dominant in the band 0.06–0.1 Hz in the large change group and in the band 0.1–0.14 Hz in the small change group. These results suggest different mechanisms related to anxiety processing in healthy individuals. One mechanism (large anxiety change) could embrace an increase of blood circulation in the territory of the left middle cerebral artery (vascular BOLD) and another (small anxiety change) translates to rhythmic central commands (neural BOLD) in the frequency band 0.1–0.14 Hz. [ABSTRACT FROM AUTHOR]

Recent advances in modeling oxygen supply to cortical brain tissue have begun to elucidate the functional mechanisms of neurovascular coupling. While the principal mechanisms of blood flow regulation after neuronal firing are generally known, mechanistic hemodynamic simulations cannot yet pinpoint the exact spatial and temporal coordination between the network of arteries, arterioles, capillaries and veins for the entire brain. Because of the potential significance of blood flow and oxygen supply simulations for illuminating spatiotemporal regulation inside the cortical microanatomy, there is a need to create mathematical models of the entire cerebral circulation with realistic anatomical detail. Our hypothesis is that an anatomically accurate reconstruction of the cerebrocirculatory architecture will inform about possible regulatory mechanisms of the neurovascular interface. In this article, we introduce large-scale networks of the murine cerebral circulation spanning the Circle of Willis, main cerebral arteries connected to the pial network down to the microcirculation in the capillary bed. Several multiscale models were generated from state-of-the-art neuroimaging data. Using a vascular network construction algorithm, the entire circulation of the middle cerebral artery was synthesized. Blood flow simulations indicate a consistent trend of higher hematocrit in deeper cortical layers, while surface layers with shorter vascular path lengths seem to carry comparatively lower red blood cell (RBC) concentrations. Moreover, the variability of RBC flux decreases with cortical depth. These results support the notion that plasma skimming serves a self-regulating function for maintaining uniform oxygen perfusion to neurons irrespective of their location in the blood supply hierarchy. Our computations also demonstrate the practicality of simulating blood flow for large portions of the mouse brain with existing computer resources. The efficient simulation of blood flow throughout the entire middle cerebral artery (MCA) territory is a promising milestone towards the final aim of predicting blood flow patterns for the entire brain. [ABSTRACT FROM AUTHOR]

To use a Doppler optical coherence tomography (DOCT) flowmeter to investigate segmental retinal blood flow (RBF) and sum of the segmental RBFs (SRBF) changes after panretinal photocoagulation (PRP) was used to treat type 2 diabetes mellitus with severe diabetic retinopathy (DR). Data from five patients with proliferative DR (PDR) (mean age 51.9 ± 10.5 years) was analyzed. The vessel diameter (D), average velocity (V), and retinal blood flow (RBF) in veins were measured using a DOCT flowmeter before and four weeks after PRP. Segmental RBF from inferotemporal (IT), superotemporal (ST), inferonasal (IN), and superonasal (SN) veins were measured, and SRBF was defined as the sum of these measurements. All data were analyzed by Wilcoxson test. After PRP, there were statistically significant decreases in the every segmental D, V, RBF (P<0.03) and SRBF (P = 0.002). The other parameters showed no statistically significant differences (P>0.05). The DOCT flowmeter has the potential to be a clinically useful tool to noninvasively evaluate the changes in retinal circulation during PRP in patients with PDR. [ABSTRACT FROM AUTHOR]

We present a one-dimensional model describing the blood flow through a moderately curved and elastic blood vessel. We use an existing two dimensional model of the vessel wall along with Navier−Stokes equations to model the flow through the channel while taking factors, namely, surrounding muscle tissue and presence of external forces other than gravity into account. Our model is obtained via a dimension reduction procedure based on the assumption of thinness of the vessel relative to its length. Results of numerical simulations are presented to highlight the influence of different factors on the blood flow. [ABSTRACT FROM AUTHOR]

Assessing potential stroke treatments in the presence of risk factors can improve screening of treatments prior to clinical trials and is important in testing the efficacy of treatments in different patient populations. Here, we test our noninvasive, nonpharmacological sensory stimulation treatment in the presence of the main risk factor for ischemic stroke, hypertension. Utilizing functional imaging, blood flow imaging, and histology, we assessed spontaneously hypertensive rats (SHRs) pre- and post-permanent middle cerebral artery occlusion (pMCAO). Experimental groups included a treatment SHR group (sensory-stimulated group), control untreated SHR group (no sensory stimulation), and a treated (sensory-stimulated) Wistar-Kyoto normotensive group. Unlike our previous studies, which showed sensory-based complete protection from impending ischemic cortical stroke damage in rats as seen in the treated Wistar-Kyoto group, we found that SHRs at 24hr post-pMCAO lacked evoked cortical activation, had a significant reduction in blood flow within the MCA, and sustained very large infarcts regardless of whether they received stimulation treatment. If translatable, this work highlights a potential need for a combined treatment plan when delivering sensory stimulation treatment in this patient population. [ABSTRACT FROM AUTHOR]

Heparin is a highly sulfated polysaccharide which belongs to the family of glycosaminoglycans. It is involved in various important biological activities. The major biological purpose is the inhibition of the coagulation cascade to maintain the blood flow in the vasculature. These properties are employed in several therapeutic drugs. Heparin’s activities are associated with its interaction to various proteins. To date, the structural heparin-protein interactions are not completely understood. This review gives a general overview of specific patterns and functional groups which are involved in the heparin-protein binding. An understanding of the heparin-protein interactions at the molecular level is not only advantageous in the therapeutic application but also in biotechnological application of heparin for downstreaming. This review focuses on the heparin affinity chromatography. Diverse recombinant proteins can be successfully purified by this method. While effective, it is disadvantageous that heparin is an animal-derived material. Animal-based components carry the risk of contamination. Therefore, they are liable to strict quality controls and the validation of effective good manufacturing practice (GMP) implementation. Hence, adequate alternatives to animal-derived components are needed. This review examines strategies to avoid these disadvantages. Thereby, alternatives for the provision of heparin such as chemical synthesized heparin, chemoenzymatic heparin, and bioengineered heparin are discussed. Moreover, the usage of other chromatographic systems mimetic the heparin effect is reviewed. [ABSTRACT FROM AUTHOR]

Background: To date there is scarce published evidence reporting the dual blood supply reaching anterior papillary muscle (APM), which descends from both major coronary arteries. Such a vascular configuration can prevent the dysfunction of right ventricular entire valvular system in case of the occlusion of proximal part of either right coronary artery (RCA) or left coronary artery (LCA). The aim of our study was to determine the vascular pattern of APM blood supply which originates from two main coronary arteries, in the context of the APM and septomarginal trabecula (SMT) topography. Methods: The study was carried out using tissue obtained from 36 human hearts. The material was divided into four morphological types of SMT/APM arrangement. Vascularization and blood supply pattern of papillary muscle was investigated following the analysis of multiple tissue cross sections. The origin of APM arterial supply was traced back to both main coronary arteries. Cross-sectional area of the arteries was estimated at the base of APM and compared within mixed male-female population, aged 18–76. Results: We noted that as much as 78% of entire APM material had a blood supply vasculature originating from both LCA and RCA branches. In contrast, 22% of cases APM was supplied by a single coronary artery, while in each case it proved to be LCA. We have never found APM arterial supply provided exclusively by RCA. In case of double AMP blood supply an average of total cross-section area of the arteries branching from LCA, was noted to be in excess of two and a half times bigger in type III and more than two times bigger in type IV, as compared with the arteries originating from RCA. Conclusions: Our research confirm the possibility of double blood supply which vascularizes APM, but the finding does not necessarily apply in all cases. However, APM seems to be predominantly vascularized by arteries deriving from LCA, regardless of their morphological type. [ABSTRACT FROM AUTHOR]

Hybrid visceral-renal debranching procedures with endovascular repair have been proposed as a less invasive alternative to conventional thoracoabdominal aortic aneurysm or dissection (TAAA or TAAD) surgery. Up to now, there has been no information about the hemodynamic effects of retrograde visceral reconstruction (RVR) for Crawford type II/III/IV TAAA patients undergoing hybrid treatment. The aim is to provide insights in the abnormal hemodynamics of RVR from unilateral or bilateral common iliac arteries (CIAs). Idealized three-dimensional AAs with RVR from unilateral CIA or bilateral CIAs were generated and computationally simulated. The results show that RVRs from CIA lead to a dramatic decrease in flow to the visceral organs compared with a healthy AA and that the anastomosis region is most dangerous to graft occlusion and the initiation of an aneurysm. In addition, compared with a quar-furcated graft, the employment of bilateral bi-furcated grafts have better performance in terms of the wall shear stress (WSS) and flow filed but result in less flow to the celiac and mesenteric arteries. This study has revealed the potential risks after an RVR operation, and points out the advantages and disadvantages of different approaches for the visceral reconstruction, which the vascular surgeons are not fully aware of. According to our results, bilateral bi-furcated grafts are recommended to the TAAA patients when the CIAs are unique inflow sites for visceral reconstruction. A precise plan with patient specific for TAAA or TAAD will be designed for better long-term outcome. [ABSTRACT FROM AUTHOR]

The mechanisms behind the clearance of soluble waste from deep within the parenchyma of the brain remain unclear. Experimental evidence reveals that one pathway for clearance of waste, termed intra-mural peri-arterial drainage (IPAD), is the rapid drainage of interstitial fluid along basement membranes (BM) of the smooth muscle cells of cerebral arteries; failure of IPAD is closely associated with the pathology of Alzheimer’s disease (AD), but its driving mechanism remains unclear. We have previously shown that arterial pulsations generated by the heart beat are not strong enough to drive IPAD. Here we present computational evidence for a mechanism for clearance of waste from the brain that is driven by functional hyperaemia, that is, the dilatation of cerebral arterioles as a consequence of increased nutrient demand from neurons. This mechanism is based on our model for the flow of fluid through the vascular BM. It accounts for clearance rates observed in mouse experiments, and aligns with pathological observations and recommendations to lower the individual risk of AD, such as mental and physical activity. Thus, our neurovascular hypothesis should act as the new working hypothesis for the driving force behind IPAD. [ABSTRACT FROM AUTHOR]

Purpose: Four‐dimensional (4D) DSA reconstruction provides three‐dimensional (3D) time‐resolved visualization of contrast bolus passage through arterial vasculature in the interventional setting. The purpose of this study was to evaluate the feasibility of using these data in measuring blood velocity and flow. Methods: The pulsatile signals in the time concentration curves (TCCs) measured at different points along a vessel are markers of the movement of a contrast bolus and thus of blood flow. When combined with the spatial content, that is, geometry of the vasculature, this information then provides the data required to determine blood velocity. A Fourier‐based algorithm was used to identify and follow the pulsatility signal. A Side Band Ratio (SBR) metric was used to reduce uncertainty in identifying the pulsatility in regions where the signal was weak. We tested this method using 4D‐DSA reconstructions from vascular phantoms as well as from human studies. Results: In five studies using 3D printed patient‐specific cerebrovascular phantoms, velocities calculated from the 4D‐DSAs were found to be within 10% of velocities measured with a flow meter. Calculated velocity and flow values from three human studies were within the range of those reported in the literature. Conclusions: 4D‐DSA provides temporal and spatial information about blood flow and vascular geometry. This information is obtained using conventional rotational angiographic systems. In this small feasibility study, these data allowed calculations of velocity values that correlated well with measured values. The availability of velocity and blood flow information in the interventional setting would support a more quantitative approach to diagnosis, treatment planning and post‐treatment evaluations of a variety of cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Background: The relationship between chronic obstructive pulmonary disease (COPD) and periprocedural complications of percutaneous coronary interventions (PCIs) is influenced by several factors. We aimed to investigate the association between COPD, its complication type and rate in patients undergoing PCI. Methods: Data were prospectively collected using the Polish Cardiovascular Intervention Society national registry (ORPKI) on all PCIs performed in Poland between January 2015 and December 2016. COPD was present in 5,594 of the 221,187 patients undergoing PCI. We assessed the frequency and predictors of periprocedural complications in PCI. Results: Patients with COPD were elder individuals (70.3 ± 9.9 vs. 67 ± 10.8 years; p < 0.05). We noted 145 (2.6%) periprocedural complications in the COPD group and 4,121 (1.9%) in the non-COPD group (p < 0.001). The higher incidence of periprocedural complications in the COPD patients was mainly attributed to cardiac arrest (p = 0.001), myocardial infarctions (p = 0.002) and no-reflows (p < 0.001). COPD was not an independent predictor of all periprocedural complications. On the other hand, COPD was found to be an independent predictor of increased no-reflow risk (odds ratio [OR] 1.447, 95% CI 1.085–1.929; p = 0.01), and at the same time, of decreased risk of periprocedural allergic reactions (OR 0.117, 95% CI 0.016–0.837; p = 0.03). Conclusions: In conclusion, periprocedural complications of PCIs are more frequent in patients with COPD. COPD is an independent positive predictor of no-reflow and a negative predictor of periprocedural allergic reactions. [ABSTRACT FROM AUTHOR]

Vasomotor response is related to the capacity of the vessel to maintain vascular tone within a narrow range. Two main control mechanisms are involved: the autonomic control of the sympathetic neural drive (global control) and the endothelial smooth cells capacity to respond to mechanical stress by releasing vasoactive factors (peripheral control). The aim of this study was to evaluate the effects of respiratory muscle training (RMT) on vasomotor response, assessed by flow-mediated dilation (FMD) and heart rate variability, in young healthy females. The hypothesis was that RMT could enhance the balance between sympathetic and parasympathetic neural drive and reduce vessel shear stress. Thus, twenty-four women were randomly assigned to either RMT or SHAM group. Maximal inspiratory mouth pressure and maximum voluntary ventilation were utilized to assess the effectiveness of the RMT program, which consisted of three sessions of isocapnic hyperventilation/ week for eight weeks, (twenty-four training sessions). Heart rate variability assessed autonomic balance, a global factor regulating the vasomotor response. Endothelial function was determined by measuring brachial artery vasodilation normalized by shear rate (%FMD/SR). After RMT, but not SHAM, maximal inspiratory mouth pressure and maximum voluntary ventilation increased significantly (+31% and +16%, respectively). Changes in heart rate variability were negligible in both groups. Only RMT exhibited a significant increase in %FMD/SR (+45%; p<0.05). These data suggest a positive effect of RMT on vasomotor response that may be due to a reduction in arterial shear stress, and not through modulation of sympatho-vagal balance. [ABSTRACT FROM AUTHOR]

Objective: This study analyzed variability in cerebral blood flow velocity (CBFV) and its association with emotional, clinical and functional variables and medication use in fibromyalgia syndrome (FMS). Methods: Using transcranial Doppler sonography, CBFV were bilaterally recorded in the anterior (ACA) and middle (MCA) cerebral arteries of 44 FMS patients and 31 healthy individuals during a 5-min resting period. Participants also completed questionnaires assessing pain, fatigue, insomnia, anxiety, depression and health-related quality of life (HRQoL). Results: Fast Fourier transformation revealed a spectral profile with four components: (1) a first very low frequency (VLF) component with the highest amplitude at 0.0024 Hz; (2) a second VLF component around 0.01-to-0.025 Hz; (3) a low frequency (LF) component from 0.075-to-0.11 Hz; and (4) a high frequency (HF) component with the lowest amplitude from 0.25-to-0.35 Hz. Compared to controls, FMS patients exhibited lower LF and HF CBFV variability in the MCAs (p < .005) and right ACA (p = .03), but higher variability at the first right MCA (p = .04) and left ACA (p = .005) VLF components. Emotional, clinical and functional variables were inversely related to LF and HF CBFV variability (r≥-.24, p≤.05). However, associations for the first VLF component were positive (r≥.28, p≤.05). While patients´ medication use was associated with lower CBFV variability, comorbid depression and anxiety disorders were unrelated to variability. Conclusions: Lower CBFV variability in the LF and HF ranges were observed in FMS, suggesting impaired coordination of cerebral regulatory systems. CBFV variability was differentially associated with clinical variables as a function of time-scale, with short-term variability being related to better clinical outcomes. CBFV variability analysis may be a promising tool to characterize FMS pathology and it impact on facets of HRQoL. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction (FGR) is associated with an increased risk for kidney disease in later life. Studies reporting on early signs of renal disturbances in FGR are sparse and mostly include invasive measurements, which limit the possibility for early identification and prevention. We aim to investigate whether renal tissue oxygen saturation (rSO2) measured with near-infrared spectroscopy (NIRS) and the derived value fractional tissue oxygen extraction (FTOE) differ between premature FGR and control neonates in the first three days after birth. Methods: Nine FGR and seven control neonates born <32 weeks of gestation were included. FGR was defined as biometry

Introduction: Arteriovenous malformations (AVMs) are characterized by pathological high flow, low resistance connections between arteries and veins. Treatment is critically dependent on correct interpretation of angioarchitectural features. However, some microfistular AVMs do not match the characteristics described in current AVM classification systems. Therefore, we propose a new subgroup of microfistular AVMs, composed of enlarged, fistulous paths on the venous half of capillaries and/or dilated draining venules (hyperdynamic, capillary-venulous malformation [CV-AVM]). CV-AVMs still ensure arterial flow to the periphery and fistulous venous drainage is less pronounced than in classical AVMs such that these lesions are often misinterpreted as venous malformations. Materials and methods: We developed a computational model to study the effects of microvascular anomalies on local hemodynamics, as well as their impact on angiographic contrast propagation. Flow rates and pressures were computed with a lumped parameter description, while contrast propagation was determined by solving the 1D advection-diffusion equation. Results and conclusions: For the newly proposed CV-AVM angioarchitecture, the computational model predicts increased arterio-venous contrast agent transit times and highly dispersive transport characteristics, compared to microfistular, interstitial type IV AVMs and high flow type II and III AVMs. We related these findings to time-contrast intensity curves sampled from clinical angiographies and found that there is strong evidence for the existence of CV-AVM. [ABSTRACT FROM AUTHOR]