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The supply of oxygen to tissues is controlled by microcirculatory blood flow. One of the more surprising discoveries in cardiovascular physiology is the critical dependence of microcirculatory blood flow on a single conserved cysteine within the β-subunit (βCys93) of hemoglobin (Hb). βCys93 is the primary site of Hb S-nitrosylation [i.e., S-nitrosothiol (SNO) formation to produce S-nitrosohemoglobin (SNO-Hb)]. Notably, S-nitrosylation of βCys93 by NO is favored in the oxygenated conformation of Hb, and deoxygenated Hb releases SNO from βCys93. Since SNOs are vasodilatory, this mechanism provides a physiological basis for how tissue hypoxia increases microcirculatory blood flow (hypoxic autoregulation of blood flow). Mice expressing βCys93A mutant Hb (C93A) have been applied to understand the role of βCys93, and RBCs more generally, in cardiovascular physiology. Notably, C93A mice are unable to effect hypoxic autoregulation of blood flow and exhibit widespread tissue hypoxia. Moreover, reactive hyperemia (augmentation of blood flow following transient ischemia) is markedly impaired. C93A mice display multiple compensations to preserve RBC vasodilation and overcome tissue hypoxia, including shifting SNOs to other thiols on adult and fetal Hbs and elsewhere in RBCs, and growing new blood vessels. However, compensatory vasodilation in C93A mice is uncoupled from hypoxic control, both peripherally (e.g., predisposing to ischemic injury) and centrally (e.g., impairing hypoxic drive to breathe). Altogether, physiological studies utilizing C93A mice are confirming the allosterically controlled role of SNO-Hb in microvascular blood flow, uncovering essential roles for RBC-mediated vasodilation in cardiovascular physiology and revealing new roles for RBCs in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if there are differences in macular capillaries between black and white subjects using optical coherence tomography angiography (OCTA) and identify potential factors underlying the epidemiologically-based higher vulnerability of black populations to diabetic retinopathy (DR). Methods: This prospective, observational cross-sectional study included 93 eyes of 47 healthy subjects with no medical history and ocular history who self-identified as black or white and were matched for age, sex, refractive error, and image quality. Subjects underwent OCTA imaging (RTVue-XR Avanti) of the superficial (SCP) and deep (DCP) capillary plexuses and choriocapillaris. AngioAnalytics was used to analyze vessel density (VD) and choriocapillaris % blood flow area (BFA) in the 1mm-diameter fovea, parafovea, and 3mm-diameter circular area including the fovea and parafovea (3x3mm image). Foveal avascular zone (FAZ) was also analyzed. Linear mixed models were used to evaluate for differences between the study groups. Results: Compared to the white subjects in this study, black subjects were found to have: lower foveal VD in the SCP (p<0.05); lower VD in the parafovea and in the 3x3mm image in the DCP (p<0.05); larger FAZ in SCP and DCP (p<0.05); and decreased choriocapillary BFA in the area underlying the fovea, parafovea, and 3x3mm image (p<0.05). Conclusion: In our study, our black subjects had decreased macular capillary vasculature compared to matched white subjects, even in early adulthood and the absence of any systemic or ocular conditions. To our knowledge, this is the first report showing that retinal and choriocapillary vascular differences may contribute to racial disparities in vulnerability to DR. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between sympathetic activity, reactive hyperemia and brachial artery flow-mediated dilation (FMD). Background: It is claimed that major surgery has an impact on endothelial function, as observed by post-operative reduced brachial artery FMD response. However, another explanation for the observed reduced FMD response post-operatively may be sympathetic stress-induced reduction in blood flow. Methods: Seventeen healthy volunteers with a median age (25th-75th percentiles) of 23.5 (23–24.8) years were recruited. Participants’ brachial blood flow and FMD response were measured (i) during normal non-stress conditions (Normal1); (ii) during exposure to ice water; and (iii) afterwards, under normal non-stress conditions (Normal2). We continuously measured arterial blood pressure (Finometer), heart rate (ECG), skin blood flow of the index finger (laser Doppler), and brachial artery blood flow and diameter (Ultrasound Doppler). Measurements were taken at baseline; before a 5-min suprasystolic forearm occlusion; and following a 3-min post-occlusion, to measure reactive hyperemia and FMD. Results: Median (25th-75th percentiles) FMD response after exposure to ice water was reduced compared to non-stress conditions [4.9 (2.9–8.4) % during ice water vs. 9.7 (7.6–12.2) % Normal1 and 9.7 (6.4–10.3) % Normal2, P < 0.001]. Blood flow 60 s after cuff-deflation during ice water exposure was significantly reduced to 328 (289–421) mL compared to non-stress conditions (both P < 0.05). No differences were observed between Normal1 [446 (359–506) mL] and Normal2 [455 (365–515) mL] (both P > 0.05). Heart rate significantly increased during ice water exposure [67 (59–69) beats/min)] compared to 55 (49–60) beats/min during Normal1 and 54 (47–60) beats/min during Normal2 (both P < 0.05). MAP did not change during Normal1 [72 (64–84)] or during Normal2 [71 (65–81) mm Hg] (both P > 0.05), but increased to 86 (75–98) mm Hg during ice water exposure (P < 0.05). Conclusions: Increased sympathetic activity resulted in decreased blood flow and brachial artery FMD response in healthy volunteers, independent of endothelial dysfunction. Future studies should adjust for blood flow when interpreting the FMD response. [ABSTRACT FROM AUTHOR]

Background: It is not clear whether the configuration of the posterior part of the circle of Willis (CW) depends on the proximal part of the vertebrobasilar system. Our aim is to evaluate the posterior part of CW in association with different size of vertebral arteries (VA) in healthy volunteers. Materials and methods: The present study was based on a sample of 923 healthy volunteers who were examined from 2013 through 2018. The duplex ultrasonographic examination of the extracranial vertebral (VA) and carotid arteries was performed. VA was defined as hypoplastic (VAH) when VA diameter in the entire course was less than 2.5 mm. All the participants underwent magnetic resonance angiography (MRA) examination. All the component vessels of the circle of Willis were assessed in each individual. We classified the posterior communicating artery (PCoA) as presence PCoA, absence/hypoplastic PCoA and fetal-type posterior circle of Willis (FCW) in which the major stem of the posterior cerebral artery (PCA) arises from ipsilateral internal carotid artery (ICA). The comparison of the posterior part of CW was made in subjects with normal VA and VAH of a different degree (communicating with basilar artery (VAH-BA) and not communicating with the basilar artery (VAH-PICA)). Results: FCW was found in 15.9% of subjects, bilaterally–in 2.3%. FCW was more frequent in individuals with VAH than in those with normal VA (accordingly, 28.8% vs. 13.5%, p<0.001. Moreover FCW was recorded in 50% of the subjects with VA—PICA in comparison with 13.5% of those with normal VA and 22.8% with VAH—BA, p<0.005. On the contrary, absence/hypoplasia of both PCoA was mostly found in the group with normal VA in comparison with VAH-BA and VAH-PICA (accordingly, 50.7%, 38.6% and 12.5%, p<0.01). Conclusion: Individuals with VAH have a different pattern of the posterior part of CW in comparison with those with normal VA. With the increasing degree of VAH, the proportion of FCW increases, while the proportion of absence/hypoplastic of both PCoA decreases. [ABSTRACT FROM AUTHOR]

Capillaries are the prime location for oxygen and nutrient exchange in all tissues. Despite their fundamental role, our knowledge of perfusion and flow regulation in cortical capillary beds is still limited. Here, we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network to investigate the impact of red blood cells (RBCs) on microvascular flow. Based on these in vivo and in silico experiments, we show that the impact of RBCs leads to a bias toward equation the values of the outflow velocities at divergent capillary bifurcations, for which we coin the term “well-balanced bifurcations”. Our simulation results further reveal that hematocrit heterogeneity is directly caused by the RBC dynamics, i.e. by their unequal partitioning at bifurcations and their effect on vessel resistance. These results provide the first in vivo evidence of the impact of RBC dynamics on the flow field in the cortical microvasculature. By structural and functional analyses of our blood flow simulations we show that capillary diameter changes locally alter flow and RBC distribution. A dilation of 10% along a vessel length of 100 μm increases the flow on average by 21% in the dilated vessel downstream a well-balanced bifurcation. The number of RBCs rises on average by 27%. Importantly, RBC up-regulation proves to be more effective the more balanced the outflow velocities at the upstream bifurcation are. Taken together, we conclude that diameter changes at capillary level bear potential to locally change the flow field and the RBC distribution. Moreover, our results suggest that the balancing of outflow velocities contributes to the robustness of perfusion. Based on our in silico results, we anticipate that the bi-phasic nature of blood and small-scale regulations are essential for a well-adjusted oxygen and energy substrate supply. [ABSTRACT FROM AUTHOR]

Chronic atherosclerosis may cause cerebral hypoperfusion and inadequate brain oxygenation, contributing to the progression of cognitive decline. In this study, we exploited two-photon phosphorescence lifetime microscopy to measure the absolute partial pressure of oxygen (PO2) in cortical tissue in both young and old LDLR-/-, hApoB100+/+ mice, spontaneously developing atherosclerosis with age. Capillary red-blood-cell (RBC) speed, flux, hematocrit and capillary diameter were also measured by two-photon imaging of FITC-labelled blood plasma. Our results show positive correlations between RBC speed, flux, diameter and capillary-adjacent tissue PO2. When compared to the young mice, we observed lower tissue PO2, lower RBC speed and flux, and smaller capillary diameter in the old atherosclerotic mice. The old mice also exhibited a higher spatial heterogeneity of tissue PO2, and RBC speed and flux, suggesting a less efficient oxygen extraction. [ABSTRACT FROM AUTHOR]

Intrarenal Doppler ultrasonography is a non-invasive method to evaluate the renal blood flow in patients with renal arterial stenosis as well as chronic kidney diseases (CKD). Until recently, the relationship between ultrasonography findings and CKD stage has not been fully understood. Overall, 162 patients with CKD without apparent renal arterial stenosis were included in this study, and the pulsed-wave Doppler ultrasonography findings were evaluated in terms of the following parameters: peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) at the renal arterial trunk, hilum, segmental, and interlobar regions. Age showed a significant negative correlation with the estimated glomerular filtration rate (eGFR), kidney size, and aortic PSV. Additionally, age showed a significant positive correlation with RI in all 4 regions. The eGFR showed a positive correlation with the aortic PSV and kidney size, but a negative correlation with RI. Both age and eGFR were found to be independently associated with aortic blood flow. On the intrarenal ultrasound, EDV and RI showed stronger correlations with eGFR than PSV, suggesting that the former indices would be better markers of renal function. In particular, the interlobar EDV was found to be the best index that reflects renal function. Although the RI is also a good marker of renal function, it is confounded by age; thus, its utility would be weaker than that of the EDV. In conclusion, intrarenal pulsed-wave Doppler ultrasonography is a useful tool to estimate and evaluate the renal function; the interlobar EDV may be the best index to estimate the effective perfusion and filtration of the kidneys. [ABSTRACT FROM AUTHOR]

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight. [ABSTRACT FROM AUTHOR]

Background: The measurement of the ankle-brachial pressure index is a straightforward method for the detection of peripheral disease in the lower limbs. Only a few old studies with small numbers of patients have been conducted comparing the gold standard, ankle-brachial pressure index measurement, with strain gauge plethysmography and reactive hyperaemia for detecting peripheral arterial disease. The purpose of this study was to evaluate the feasibility and accuracy of strain gauge plethysmography values compared with the Doppler ultrasound method, ankle-brachial pressure index, in the assessment of peripheral arterial disease, especially in patients with severe aortic stenosis. Methods: 221 ankle-brachial pressure index measurements and strain gauge plethysmography measurements of patients with suspected peripheral arterial disease, diagnosed peripheral arterial disease with or without aortic stenosis were compared. Results: Irrespective of aortic stenosis in patients with and without peripheral arterial disease, the resting arterial blood flow was within the normal range. In patients with aortic stenosis, the time-to-peak flow couldn’t detect peripheral arterial disease and was found to be a false negative. In patients without aortic stenosis, time-to-peak flow correlated well with the ankle-brachial pressure index for detecting peripheral arterial disease. Peak flow at 5 seconds was the one of the flow values that correlated with ankle-brachial pressure index and detected peripheral arterial disease in patients with and without aortic stenosis. Conclusion: Peak flow at 5 seconds is one of flow value that correlated well with ankle-brachial pressure index in detecting peripheral arterial disease in patients with and without aortic stenosis. Detection of peripheral arterial disease in patients with severe aortic stenosis seems to be less sensitive with flow measurements than with ankle-brachial pressure index. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Background: Arterial graft spasm is a severe complication after coronary artery bypass graft (CABG). Among numerous potential antispasmodic agents, systemic application of diltiazem and nitroglycerin had been investigated most frequently over the past three decades. However, it remains inconclusive if either or both agents could improve patient outcomes by preventing graft spasm when applied perioperatively, and, if so, which one would be a better choice. The current systematic review and network meta-analysis aims to summarize the data from all available randomized clinical trials of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing on-pump CABG in order to define and compare their roles in graft spasm prevention and their impacts on perioperative outcomes. Methods: We searched Ovid Medline, PubMed, CINAHL, Google Scholar and Cochrane Center for randomized controlled trials that reported outcome effects of perioperative continuous intravenous infusion of diltiazem and/or nitroglycerin in patients undergoing elective on-pump CABG. Conventional meta-analyses were conducted to evaluate the pairwise comparisons (diltiazem vs. placebo; nitroglycerin vs. placebo; diltiazem vs. nitroglycerin) on perioperative outcomes. Network meta-analyses were implemented to compare the three regimens through direct and indirect comparison. Results: Twenty-seven studies involving 1,660 patients were included. Pairwise and network meta-analyses found no significant difference in mortality among the groups. There are four studies that reported blood flow measurements of internal mammary artery grafts intraoperatively after dissecting or immediately after distal anastomosis while patients were on continuous intravenous infusion of diltiazem and nitroglycerin. Although insufficient for data synthesis, the measured results from all four studies suggest that both diltiazem and nitroglycerin significantly increased blood flow of arterial grafts compared to placebo. For other perioperative outcomes, compared to diltiazem, patients that received nitroglycerin had higher odds of postoperative atrial fibrillation (OR = 2.67, 95% CI: 1.15 to 6.24) and higher peak serum cardiac enzymes. Patients that received placebo had higher odds of atrial fibrillation (OR = 3.00, 95% CI: 1.18 to 7.63) and lower odds of requiring inotrope support (OR = 0.19, 95% CI: 0.04 to 0.73) compared to diltiazem. Data from the network meta-analysis indicated that diltiazem had significantly lower odds of postoperative atrial fibrillation compared to nitroglycerin (OR = 0.39, 95% CI: 0.18 to 0.85). In fact, the rank from highest to lowest rates of postoperative atrial fibrillation was placebo>nitroglycerin>diltiazem. The rank from highest to lowest odds of requiring inotropic support is nitroglycerin> diltiazem>placebo. However, placebo had significantly higher odds of postoperative myocardial infarction than diltiazem (OR = 4.51, 95% CI: 1.34 to 15.25). The rank from highest to lowest odds of postoperative myocardial infarction, transient cardiac ischemic event and atrial fibrillation is placebo>nitroglycerin>diltiazem. Conclusion: Compared to nitroglycerin and placebo, perioperative continuous intravenous infusion of diltiazem had stronger protective effects against postoperative ischemic cardiac injuries and atrial fibrillation although patients may need more inotropic support. The increased blood flow from diltiazem use in arterial grafts may potentially contribute to the drug’s outcome benefits. [ABSTRACT FROM AUTHOR]

An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) computational aortic models have been established to reproduce aortic diseases such as aortic aneurysm and dissection; however, no such models have been developed to study diabetes mellitus (DM). To characterize biomechanical properties of the human aorta with DM, reconstructed aortic CT images were converted into DICOM format, and imported into the 3D segmentation using Mimics software. This resulted in a 3D reconstruction of the complete aorta, including three branches. We applied a pulsatile blood pressure waveform for the ascending aorta to provide a biomimetic environment using COMSOL Multiphysics software. Hemodynamics were compared between the control and DM models. We observed that mean blood flow velocity, aortic pressure, and von Mises stress values were lower in the DM model than in the control model. Furthermore, the range of aortic movement was lower in the DM model than in the control model, suggesting that the DM aortic wall is more susceptible to rupture. When comparing biomechanical properties in discrete regions of the aorta, all values were higher in the ascending aorta for both control and DM models, corresponding to the location of most aortic lesions. We have developed a compute based that integrates advanced image processing strategies and computational techniques based on finite element method to perform hemodynamics analysis based on CT images. Our study of image-based CFD analysis hopes to provide a better understanding of the relationship between aortic hemodynamic and developing pathophysiology of aortic diseases. [ABSTRACT FROM AUTHOR]

Background: In the presence of a coronary occlusion, pre-existing small collateral vessels (arterioles) develop into much larger arteries (biological bypasses) that have the potential to allow a certain level of perfusion distal to the blockage. Termed arteriogenesis, this phenomenon proceeds via a complex combination of events, with nitric oxide (NO) playing an essential role. The aim of this study was to investigate the effects of supplemental administration of NO donors, i.e., short-acting nitroglycerin (NTG) or slow-release pelleted isosorbide dinitrate (ISDN), on collateral development in a repetitive coronary artery occlusion model in rats. Methods: Coronary collateral growth was induced via a repetitive occlusion protocol (ROP) of the left anterior descending coronary artery (LAD) in rats. The primary endpoints were the histological evaluation of rat heart infarct size and ST-segment elevation (ECG-analysis) upon final permanent occlusion of the LAD (experimentally induced myocardial infarction). The effects of NTG or ISDN were also evaluated by administration during 5 days of ROP. We additionally investigated whether concomitant application of NTG can compensate for the anti-arteriogenic effect of acetylsalicylic acid (ASA). Results: After 5 days of ROP, the mean infarct size and degree of ST-elevation were only slightly lower than those of the SHAM group; however, after 10 days of the protocol, the ROP group displayed significantly less severe infarct damage, indicating enhanced arteriogenesis. Intermittent NTG application greatly decreased the ST-elevation and infarct size. The ISDN also had a positive effect on arteriogenesis, but not to the same extent as the NTG. Administration of ASA increased the infarct severity; however, concomitant dosing with NTG somewhat attenuated this effect. Conclusion: Intermittent treatment with the short-acting NTG decreased the size of an experimentally induced myocardial infarct by promoting coronary collateral development. These new insights are of great relevance for future clinical strategies for the treatment of occlusive vascular diseases. [ABSTRACT FROM AUTHOR]

One-compartment models are widely used to quantify hemodynamic parameters such as perfusion, blood volume and mean transit time. These parameters are routinely used for clinical diagnosis and monitoring of disease development and are thus of high relevance. However, it is known that common estimation techniques are discretization dependent and values can be erroneous. In this paper we present a new model that enables systematic quantification of discretization errors. Specifically, we introduce a continuous flow model for tracer propagation within the capillary tissue, used to evaluate state-of-the-art one-compartment models. We demonstrate that one-compartment models are capable of recovering perfusion accurately when applied to only one compartment, i.e. the whole region of interest. However, substantial overestimation of perfusion occurs when applied to fractions of a compartment. We further provide values of the estimated overestimation for various discretization levels, and also show that overestimation can be observed in real-life applications. Common practice of using compartment models for fractions of tissue violates model assumptions and careful interpretation is needed when using the computed values for diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]

Background and purpose: Arterial spin labeling(ASL)with magnetic resonance imaging (MRI) is an effective method for estimating cerebral blood flow (CBF). Furthermore, assessing perfusion territories of arteries is useful for determining the treatment strategy of patients with carotid artery stenosis. ASL with selective vessel labeling is an effective method to obtain perfusion mapping, however, the application for selective labeling is not installed on all MR scanners. The purpose of this study is to establish a method to selectively mask in the labeling area using material with high susceptibility instead of selectively labeling to obtain a partial perfusion image. Materials and methods: ASL perfusion images were performed in five volunteers. Masking was applied by placing a stainless-steel bolt and nuts on the neck. The area of artifacts extended to the carotid artery was confirmed by the localizer image. In the obtained masked ASL, blood flow of the left and right cerebrum and cerebellum was measured and compared with control ASL without masking. By subtracting masked ASL from the control ASL, the perfusion territory of the carotid artery on the masked side was identified. Results: Mean CBF which was 39.6 ml/(100 g × min) in control ASL decreased to 16.1 ml/(100 g × min) in masked ASL, and the masking ratio was 59.6%. There were no significant differences in the CBF of non-masked areas under the control ASL condition (39.6± 5.2 ml/[100 g × min]) btween that under the masked ASL condition (39.4 ± 7.0 ml/[100 g × min]). By subtracting masked ASL from control ASL, we successfully visualized the hemilateral carotid artery’s perfusion territory. Conclusion: Intentional susceptibility artifacts with non-magnetic metals on the neck can mask spin labeling of the carotid artery. Furthermore, hemilateral carotid artery perfusion territories can be visualized in hemilaterally masked ASL. [ABSTRACT FROM AUTHOR]

Background: Caffeine is routinely given to preterm infants hours after birth to treat apnea of prematurity. In view of it’s success, earlier administration in the delivery room is being considered, but little is known about how caffeine may effect the cardiovascular changes during the fetal to neonatal transition. Our aim was to determine the effect of prenatal caffeine administration on haemodynamic parameters in ventilated preterm lambs immediately after birth. Methods: Catheters (carotid artery and jugular vein) and ultrasonic flow probes (pulmonary artery and carotid artery) were implanted in preterm lambs (~126 ±2 days of gestation; term is 147 days), immediately before delivery by caesarean section. Before the cord was clamped, lambs were intubated and a caffeine (10mg/kg caffeine-base; n = 9) or saline (n = 5) infusion was given intravenously to the ewe and lamb over a 15-minute period. Two minutes after clamping the cord, ventilation commenced with a sustained inflation (35 cm H2O for 30 seconds) followed by ventilation for 30 minutes (target tidal volume of 6-8ml/kg). Results: Blood gas parameters and rectal body temperature were not different between the two groups. Changes in pulmonary blood flow (PBF) and carotid blood flow (CBF) did not differ significantly between groups. PBF increased significantly after ventilation onset in both groups (caffeine p = 0.022, saline p <0.001) and remained elevated thereafter. CBF did not increase but decreased after SI in the caffeine group. Blood pressure, heart rate, and peripheral oxygen saturation did not differ between groups at any stage of the study. Conclusion: Prenatal caffeine infusion had no significant effect on acute haemodynamic parameters in ventilated preterm lambs during the cardiorespiratory transition. [ABSTRACT FROM AUTHOR]

Drug delivery to the brain is challenging due to the presence of the blood-brain barrier. Mathematical modeling and simulation are essential tools for the deeper understanding of transport processes in the blood, across the blood-brain barrier and within the tissue. Here we present a mathematical model for drug delivery through capillary networks with increasingly complex topologies with the goal to understand the scaling behavior of model predictions on a coarse-to-fine sequence of grids. We apply our model to the delivery of L-Dopa, the primary drug used in the therapy of Parkinson’s Disease. Our model replicates observed blood flow rates and ratios between plasma and tissue concentrations. We propose an optimal network grain size for the simulation of tissue volumes of 1 cm3 that allows to make reliable predictions with reasonable computational costs. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN. [ABSTRACT FROM AUTHOR]