Fluctuations In Blood Flow Research Articles

Application of laser speckle blood perfusion imaging in the evaluation of erectile function in rats.

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n=30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5V. Cavernous blood flow fluctuation in the model group after 2.5V, 5V and 7.5V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.

A Prospective Study to Investigate Controlling Blood Pressure Under Transcranial Doppler After Endovascular Treatment in Patients With Occlusion of Anterior Circulation.

Objective: The objective of this study was to evaluate the effect of blood pressure (BP) management with transcranial Doppler (TCD) guidance in patients with large-vessel occlusion in the anterior circulation after endovascular thrombectomy (EVT) on the long-term prognosis.Methods: This was a prospective study; 232 patients were nonrandomized assigned to TCD-guided BP management (TBM) group or non-TCD-guided BP management (NBM) group. In the TBM group, BP was controlled according to TCD showing cerebral blood flow fluctuation. In the NBM group, BP was controlled according to the guidelines. The primary endpoint was a modified Rankin scale (mRS) score of 2 or lower at 90 days. The safety outcomes were the rates of symptomatic or any intracerebral hemorrhage (ICH) and mortality at 90 days.Results: One hundred sixty-three patients were assigned to the TBM group, and 69 were assigned to the NBM group. In the propensity score-matched cohort (65 matches in both groups), there was significant difference in the proportion of participants with mRS 0–2 at 90 days according to BP management (adjusted odds ratio 3.34, 95% CI 1.36 to 8.22). There was no difference in the rates of symptomatic or any ICH and mortality between two groups. In inverse probability-weighted regression adjustment analysis, mortality decreased significantly in the TBM group than in the NBM group (adjusted odds ratio 0.86, 95% CI 0.76–0.99, p = 0.03).Conclusion: In patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation, BP management under TCD was superior to NBM in improving the clinical outcomes at 90 days.Clinical Trial Registration: (URL: https://www.chictr.org.cn/showproj.aspx?proj=55484; Identifier: ChiCTR2000034443.

Laser doppler flowmetry assessment of microcirculation in children of 6–7 years old

Introduction.The state of the blood flow within the capillaries and close blood vessels is highly important in practice for the revealing of pathogenetic mechanisms of both systemic and local circulatory disorders.Aimof the study was to define the parameters of microcirculation and the level of blood flow fluctuations (flux) in the distal segments of upper and lower limbs (in fingers of hands and toes of feet) in children of 6–7 years old; and to describe the possible differences in the mechanisms of blood flow modulation in boys and girls.Materials and methods.Skin microcirculation was assessed in middle fingers of hands and great toes of feet in children of 6-7 years old (14 girls and 7 boys in prone position) by means of laser doppler flowmetry.Results.The ranges for parameters of microcirculation (PM) for distal segments of upper and lower limbs in children of mentioned age group were defined, also it was shown that the PM are significantly lower in the lower limbs comparing to those of the upper limbs (both in groups of girls and boys). Asymmetry of PM in the feet was not found; the features of right hand-left hand asymmetry for PM in girls and boys are described. The analysis of modulation of blood flow fluctuations (fluxmotions) of different frequencies showed the profound role of vasomotor (myogenic) rhythm for regulation of microcirculation.Conclusion.Increased neurogenic influences on the modulation of fluxmotions in girls of 6-7 years old may be an evidence of the ongoing development of the mechanisms of blood flow regulation, particularly the association with the growth rate of girls is possible.

Assessment of flow within developing chicken vasculature and biofabricated vascularized tissues using multimodal imaging techniques

Fluid flow shear stresses are strong regulators for directing the organization of vascular networks. Knowledge of structural and flow dynamics information within complex vasculature is essential for tuning the vascular organization within engineered tissues, by manipulating flows. However, reported investigations of vascular organization and their associated flow dynamics within complex vasculature over time are limited, due to limitations in the available physiological pre-clinical models, and the optical inaccessibility and aseptic nature of these models. Here, we developed laser speckle contrast imaging (LSCI) and side-stream dark field microscopy (SDF) systems to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocytes movements within individual blood vessels of developing chick embryo, cultured within an artificial eggshell system. By combining imaging data and computational simulations, we estimated fluid flow shear stresses within multiscale vasculature of varying complexity. Furthermore, we demonstrated the LSCI compatibility with bioengineered perfusable muscle tissue constructs, fabricated via molding techniques. The presented application of LSCI and SDF on perfusable tissues enables us to study the flow perfusion effects in a non-invasive fashion. The gained knowledge can help to use fluid perfusion in order to tune and control multiscale vascular organization within engineered tissues.

End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn \u2013 an observational cohort study

BackgroundNear-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO.MethodsNewborns < 29 weeks’ gestation (2013–2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers.ResultsForty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3 ± 3.8 weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE.ConclusionsNIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.

Similar Effects of an Orexin Receptor Antagonistand Benzodiazepine Receptor Agonist on Cerebral Blood Flow Regulation

Orexin receptor antagonists have a different sleep-inducing mechanism from common hypnotic benzodiazepinereceptor agonists. Thus, orexin receptor antagonists may affect cerebral circulation differently, although theireffects have rarely been investigated. In this study, the effects of an orexin receptor antagonist on cerebral bloodflow regulation were compared with those of a benzodiazepine, including dynamic cerebral autoregulation. Fifteenhealthy males received suvorexant (1 tablet, 20 mg), an orexin receptor antagonist, and brotizolam (1 tablet, 0.25mg), a benzodiazepine receptor agonist, in a randomized order at least 7 days apart. Before and 1.5 h after drugadministration, arterial blood pressure and cerebral blood flow velocity were measured by transcranial Doppler ina supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between mean arterial blood pressure variability and mean cerebral blood flow velocity variability. The steady-state mean cerebralblood flow velocity decreased significantly with both suvorexant and brotizolam (significant main effect of time,P = 0.003) and was associated with unchanged steady-state mean arterial blood pressure. Moreover, transfer function gain in the low- and high-frequency ranges were decreased significantly by both suvorexant and brotizolam(significant main effect of time, P < 0.001), suggesting a decrease in the magnitude of transfer from arterial bloodpressure oscillations to cerebral blood flow fluctuations. These changes were not significantly different betweensuvorexant and brotizolam (no significant interaction effect). The present results indicate that suvorexant andbrotizolam, two different types of hypnotic drug, have similar effects on cerebral blood flow regulation, includingpossible improvements in dynamic cerebral autoregulation with decreased steady-state cerebral blood flow.

Elephant Seal Endothelial Cells are Resistant to Oxidative Stress

Marine mammals experience acute fluctuations in blood flow and oxygen content while diving. In humans and other non-diving species, fluctuations of similar magnitude (e.g., during ischemia/reperfusion events) increase reactive oxygen species generation and oxidative damage. Endothelial cells are particularly susceptible to reperfusion injury, which is associated with vascular pathologies including myocardial infarction and ischemic stroke. Marine mammals, however, are protected against reperfusion injuries, though the precise cellular mechanisms driving this protection remain unclear. To study this phenomenon, we isolated placental arterial endothelial cells from humans and northern elephant seals. Elephant seals are elite divers with extreme hypoxemic tolerance. Seal and human endothelial cells express canonical endothelial cell markers (PECAM-1, VE-cadherin) and respire under basal culture conditions. Seal endothelial cells have lower proton leak and higher respiratory capacity than human cells and respond to pharmacological stimulation of NADPH oxidase. Hypoxia/reoxygenation or treatment with menadione increases oxidant generation in human cells by 5-fold (p=0.027) but not in seal cells (2.5-fold, p=0.18). Similarly, lipid peroxidation increases 2-fold in human (p=0.0002) but not seal (p=0.19) cells treated with organic peroxides, despite lower protein abundance of the phospholipid hydroperoxidases peroxiredoxin 6 (Prdx6) and glutathione peroxidase 4 (Gpx4) in seal cells. These results demonstrate that seal cells possess an intrinsic capacity to cope with oxidants. Moreover, these results highlight the translational potential of identifying the mechanisms driving seals’ natural tolerance to ischemia/reperfusion events.

Состояние гемодинамики и вариабельность сердечного ритма у тяжелобольных COVID‑19 в разгар заболевания и в процессе реабилитации

Введение. Состояние системы гемостаза при COVID-19 детально исследовано. Вместе с тем совершенно не изучено состояние гемодинамики и вариабельность сердечного ритма (ВСР) у больных COVID-19 в разгар заболевания и в процессе реабилитации. Цель исследования: изучить состояние микроциркуляции и ВСР у больных с тяжелым течением COVID-19 в процессе заболевания, после выписки из стационара и после прохождения курса реабилитации. Материалы и методы. Наши наблюдения проведены на 43 пациентах, получавших лечение в ГУЗ «ГКБ № 1» (Чита), перепрофилированной для терапии больных COVID-19, а также на курорте «Дарасун» (Забайкальский край), предназначенном для реабилитации больных, перенесших COVID-19. Контрольную группу составили 69 человек, сопоставимых по полу возрасту и сопутствующим заболеваниям. Состояние кровотока и ВСР изучали с помощью датчика mDLS (Dynamic Light Scattering, Rehovot, Israel) и использования оригинального алгоритмического подхода. При этом сигнал разлагался на частотные компоненты, связанные с гемодинамическими источниками различной скорости сдвига слоев крови (гемодинамические индексы), в значительной степени отражающих состояние системы гемостаза. Результаты. У больных COVID‑19 абсолютные значения гемодинамических индексов оказались значительно выше, чем в контроле, что свидетельствует об усилении микроциркуляторной динамики. Особенно резко возрастали значения HI1и HI2, что связано с усилением пристеночного (эндотелиального) и промежуточного кровотока. Об этом же свидетельствует увеличение у тяжелобольных почти в 4 раза соотношения HI1/HI3, которое не восстанавливалось после выздоровления, а также после реабилитации. Одновременно в разгар заболевания происходило значительно усиление пульсовых (PULSE 1 и 2) и резкое снижение респираторных (RESP1, 2 и 3) осцилляторных индексов, значения которых оставались стабильными как у выздоровевших пациентов, так и у прошедших курс реабилитации. Заключение. У больных COVID-19 в разгар заболевания отмечаются выраженные сдвиги со стороны микроциркуляции и ВСР, обусловленные повышением тонуса симпатического отдела автономной нервной системы, и сохраняющееся после выписки из стационара и прохождения курса реабилитации. Background. Hemostasis in COVID‑19 has been studied in detail. The state of hemodynamics and heart rate variability (HRV) in patients with COVID‑19 at the height of the disease and during rehabilitation has not been fully studied. Objectives: to study microcirculation and HRV in patients with severe COVID-19 during the course of the disease, after discharge from the hospital and after rehabilitation course. Patients/Methods. We examined 43 patients with COVID‑19 treated at City Clinical Hospital № 1 (Chita) and underwent rehabilitation at Darasun resort (Trans-Baikal Territory). The control group consisted of 69 people of same sex, age and concomitant diseases. Blood flow and HRV were studied using mDLS sensor (Dynamic Light Scattering, Rehovot, Israel) and an original algorithmic approach. The signal was decomposed into frequency components associated with hemodynamic sources of different shear rates of blood layers (hemodynamic indexes) that largely reflected hemostasis state. Results. In patients with COVID-19, the absolute values of hemodynamic indexes were significantly higher than in controls, it was the evidence of microcirculatory intensification. The HI1 and HI2 values increased especially sharply, that was associated with increased endothelial and intermediate blood flow. This was also evidenced by an almost 4‑fold increase in the HI1/HI3 ratio in seriously ill patients that does not restored after recovery, as well as after rehabilitation. At the same time, at the height of the disease, there was a significant increase of pulse (PULSE 1 and 2) and a sharp decrease of respiratory (RESP1, 2 and 3) oscillatory indexes, that remained stable both in recovered patients and in those who underwent a course of rehabilitation. Conclusions. In patients with COVID-19 at the height of the disease pronounced shifts in microcirculation and HRV are noted due to increased tonus of sympathetic nervous system that persisted after discharge and rehabilitation.

Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey

BackgroundMetabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs.MethodsA questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018.ResultsThe survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs).ConclusionThis survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

Mapping the orbitofrontal cortex using temporal fluctuations in cerebral blood flow

IntroductionThe orbitofrontal cortex (OFC) is involved in diverse cognitive and behavioral processes including incentive valuation, decision‐making, and reinforcement learning. Anatomic and cytoarchitectonic studies divide the OFC along both medial‐lateral and rostral‐caudal axes. OFC regions diverge in structure and function, assessed in vivo using white matter tractography and blood oxygenation level‐dependent (BOLD) MRI, respectively. However, interpretation of T 2*‐weighted BOLD is limited by susceptibility artifacts in the inferior frontal lobes, with the spatial pattern of these artifacts frequently assuming the geometry of OFC organization. Here, we utilize a novel perfusion‐weighted arterial spin labeling (ASL) functional connectivity approach, which is minimally susceptibility‐weighted, to test the hypothesis that OFC topology reflects correlated temporal hemodynamic activity.MethodsIn healthy participants (n = 20; age = 29.5 ± 7.3), 3D ASL scans were acquired (TR/TE = 3,900/13 ms; spatial resolution = 3.8 mm isotropic). To evaluate reproducibility, follow‐up scanning on a separate day was performed on a participant subset (n = 8). ASL‐based connectivity was modeled for gray matter OFC voxels, and k‐means clustering (k = 2–8) applied to correlation statistics.ResultsThese approaches revealed both medial‐lateral and rostral‐caudal OFC divisions, confirming our hypothesis. Longitudinal reproducibility testing revealed 84% voxel clustering agreement between sessions for the k = 2 solution.ConclusionTo our knowledge, this constitutes the first in vivo cortical parcellation based on perfusion fluctuations. Our approach confirms functional OFC subdivisions predicted from anatomy using a less susceptibility‐sensitive method than the conventional approach.

Developmental Coupling of Cerebral Blood Flow and fMRI Fluctuations in Youth

To support brain development during youth, the brain must balance energy delivery and consumption. Previous studies in adults have demonstrated high coupling between cerebral blood flow and brain function as measured using functional neuroimaging, but how this relationship evolves over adolescence is unknown. To address this gap, we studied a sample of 831 children and adolescents (478 females, ages 8-22) from the Philadelphia Neurodevelopmental Cohort who were scanned at 3T with both arterial spin-labeled (ASL) MRI and resting-state functional MRI (fMRI). Local coupling between cerebral blood flow (CBF, from ASL) and the amplitude of low frequency fluctuations (ALFF, from fMRI) was first quantified using locally weighted regressions on the cortical surface. We then used generalized additive models to evaluate how CBF-ALFF coupling was associated with age, sex, and executive function. Enrichment of effects within canonical functional networks was evaluated using spin-based permutation tests. Our analyses revealed tight CBF-ALFF coupling across the brain. Whole-brain CBF-ALFF coupling decreased with age, largely driven by coupling decreases in the inferior frontal cortex, precuneus, visual cortex, and temporoparietal cortex (pfdr<0.05). Furthermore, we found that females had stronger coupling in the frontoparietal network than males (pfdr<0.05) and that better executive function was associated with decreased coupling in the somatomotor network (pfdr<0.05). These results emphasize that CBF-ALFF coupling undergoes development in youth and is linked to individual differences in cognition. As such, this relationship may be a valuable marker of both normal brain development and abnormalities associated with neuropsychiatric illness in youth.

Assessment of Motor Cortex in Active, Passive and Imagery Wrist Movement Using Functional MRI.

Background: Functional Magnetic resonance imaging (fMRI) measures the small fluctuation of blood flow happening during task-fMRI in brain regions.Objective: This research investigated these active, imagery and passive movements in volunteers design to permit a comparison of their capabilities in activating the brain areas.Material and Methods: In this applied research, the activity of the motor cortex during the right-wrist movement was evaluated in 10 normal volunteers under active, passive, and imagery conditions. T2* weighted, three-dimensional functional images were acquired using a BOLD sensitive gradient-echo EPI (echo planar imaging) sequence with echo time (TE) of 30 ms and repetition time (TR) of 2000 ms. The functional data, which included 248 volumes per subject and condition, were acquired using the blocked design paradigm. The images were analyzed by the SPM12 toolbox, MATLAB software.Results: The findings determined a significant increase in signal intensity of the motor cortex while performing the test compared to the rest time (p< 0.05). It was also observed that the active areas in hand representation of the motor cortex are different in terms of locations and the number of voxels in different wrist directions. Moreover, the findings showed that the position of active centers in the brain is different in active, passive, and imagery conditions. Conclusion: Results confirm that primary motor cortex neurons play an essential role in the processing of complex information and are designed to control the direction of movement. It seems that the findings of this study can be applied for rehabilitation studies.

АНАЛИЗ ЛДФ-ГРАММ У КРЫС СТОКА WISTAR В УСЛОВИЯХ МОДЕЛИРОВАНИЯ ГИПОКСИИ

The aim of the study was to assess the dynamics of the change in peripheral blood flow parameters of the blood vessels of the microcirculatory bed of the skin, with an additional analysis of the change in the amplitude of the frequency ranges of cutaneous blood flow, in the conditions of daily interval hypobaric training by laser Doppler flowmetry. The effect of interval hypobaric training course (seven days duration, exposure duration was 60 minutes) on the state of the microcirculatory bed of the skin was investigated to study the peculiarities of the formation and course of adaptive reactions in the vessels of the microcircuit. An analysis of microcirculation indicators using LDF diagnostics was carried out. Hardware – laser analyzer of capillary circulation «LACC-02» manufactured by LLC NPP «Lasma,» Moscow. The main basal blood flow indicators and microcirculation indicators were revealed when exposed to a 7-day course of interval hypobaric training. The statistical values of PM (constant perfusion parameter, units), σ (mean square deviation of amplitude of perfusion fluctuation, units) and Kv (coefficient of variation, %) provided an opportunity to analyze the general state of blood microcirculation. The amplitude-frequency spectrum of perfusion oscillations was also evaluated. With the help of a wavelet analysis (program 2.2.0.507, NPP Lasma, Russia), normalized amplitudes of blood flow fluctuations in frequency ranges were determined (endothelial due to nitric oxide activity (0.0095–0.02 Hz); neurogenic (0.02–0.06 Hz); myogenic (vasomosis) (0.06–0.2 Hz) and passive frequency range (cardiac (0.6–1.6 Hz), respiratory (0.2–0.6 Hz). Measurement of microcirculation parameters was carried out 3 times at the following stages of the experiment: before hypoxic exposure – point 0 (8 minutes), on the 1st day immediately after hypoxia exposure (8 minutes), and on the 7th day immediately after hypoxia session (8 minutes). The measurement area was the inner surface of the lower pelvic limb, the LDF sensor was located on the surface of the skin. The recording duration was 360 seconds. The hypoxic effect used in the study was implemented using hardware – an experimental hypobarocamera, in which the necessary conditions were created (negative pressure (–0.306kg/cm2)). The pressure in the chamber was reduced in stages: the first stage – a height of 1000 m with air dilution (–0.1 kg/cm2), duration 180 seconds; second stage – 2000 m rarefaction was (–0.21 kg/cm2) with the same duration; and the last stage is 3000 m high, which corresponds to a vacuum (–0.306 kg/cm2). A seven-day course of hypoxia did not cause significant changes in cutaneous blood flow in animals in group C (control), and in animals in group P (pseudo-hypoxic rats). However, it was found that in rats in group H (hypoxia) there was an increase in the coefficient of variation by 62.5 % (p≤ 0.05) on the 7th day of exposure, this may be due to the launch of adaptation mechanisms, which are necessary to adequately supply blood to cells, tissues and organs. When analyzing LDF-grams in rats of group C (control) and P (pseudo-hypoxed), there was no change in the perfusion parameter in the microcirculatory channel, but in group G (hypoxia) – PM (microcirculation index) significantly decreased by 47 % (p&lt;0.05). In animals of groups C (control) and P (psvedo-hypoxed), there were no significant changes, according to the data of the wavelet analysis. However, in group H rats (hypoxia) on the 1st day of exposure, there was an increase in the frequency of the amplitude of oscillations in the myogenic range (0.06–0.2 Hz) on 18.72 % (p &lt; 0.05) and passive frequency ranges (cardiac modulating factor (0.6–1.6 Hz) in the LDF-gram of the subjects on 14.97 % (p&lt;0.05). Summing up the above, the results of the analysis of LDF-grams and the microcirculation index (PM) made it possible to establish a significant role in the possible use of the LDF-diagnostic method to evaluate the quality of methods for increasing the adaptive capabilities of the vessels of the skin microcirculatory bed and also central vessels. The dynamics of the frequency ranges of the vessels of nutritive blood flow in rats after a weekly course of interval hypobaric changed as follows: the role of passive factors, mainly the pulse wave from the arterial link, was increased by 24 % (p&lt;0.05). The observed changes can be related to the enhancement of muscle cells in the vascular wall of the arterial vessels of the skin microcirculatory system, and as a result, the enhancement of the functioning of the circulatory system. By laser Doppler flowmetry, the dynamics of changes in peripheral circulatory indices were investigated with the assessment of changes in rats, with the study of the frequency ranges of cutaneous blood.

The impact of age and sex on popliteal artery endothelial-dependent vasodilator and vasoconstrictor function.

Lower-limb arteries, such as the popliteal artery, are a common site of atherosclerosis. These arteries are habitually exposed to large fluctuations in blood flow during physical and sedentary activities. Low-flow-mediated constriction (L-FMC) and flow-mediated dilation (FMD) provide indices of endothelial-dependent vasoconstriction and vasodilation, respectively. Age and sex both impact upper-limb FMD. However, it is unclear whether these factors also influence popliteal endothelial-dependent function. Popliteal endothelial function was compared between younger and older males and females (n=14 per group) matched for age- and sex-specific relative aerobic fitness levels (each group's normative percentile: ~45%). Nitroglycerin-mediated dilation (NMD) was also assessed as a measure of endothelial-independent vasodilation. Ageing reduced relative popliteal FMD in both males (older: 4.3±1.8% versus younger 5.7±1.9%) and females (older: 2.9±1.8% versus younger: 6.1±1.6%, both: P<0.046). FMD was also lower in older females versus older males (P=0.04). Popliteal NMD findings followed the same pattern as FMD. Compared to younger adults, relative L-FMC responses were blunted among older males (older: -1.2±1.1% versus younger: -2.2±1.0%) and females (older: -1.0±1.2% versus younger: -2.1±1.3%, both P<0.03) with no sex-differences observed in either age group (all, P>0.60). The adverse age- and sex-related (older adults only) declines in popliteal FMD were mediated, in part, by reduced vascular smooth muscle sensitivity to nitric oxide. Endothelial-dependent vasoconstriction was also attenuated with age, but unaffected by sex. Despite similar normative aerobic fitness percentiles (~45%), older adults exhibited attenuated popliteal endothelial function than their younger counterparts. This was particularly evident in older females who exhibited the lowest endothelial-dependent vasodilatory responses.

Orthostatic Headache in Children Including Postural Tachycardia Syndrome and Orthostatic Hypotension: A Near-Infrared Spectroscopy Study.

Background and aim: Although head and/or neck pain attributed to orthostatic hypotension is included in international guidelines, its mechanisms and relevance remain unknown. This study examined the term’s relevance and aimed to elucidate the associated clinical features. Methods: An active stand test was performed to evaluate fluctuations in systemic and cerebral circulation in children and adolescents reporting complaints in the absence of a confirmed organic disorder. The subjects were categorized based on orthostatic headache presence/absence, and their characteristics and test results were compared. Results: Postural tachycardia syndrome was observed in 50.0% of children with, and 55.1% without, orthostatic headache. For orthostatic hypotension, the respective values were 31.3% and 30.6%. A history of migraine was more prevalent in children with orthostatic headaches (64.1% vs. 28.6%; p < 0.01). The observed decrease in the cerebral oxygenated hemoglobin level was larger in children with orthostatic headaches (Left: 6.3 (3.2–9.4) vs. 4.1 (0.8–6.1); p < 0.01, Right: 5.3 (3.1–8.6) vs. 4.0 (0.8–5.9); p < 0.01). Conclusion: Fluctuations in cerebral blood flow were associated with orthostatic headaches in children, suggesting that the headaches are due to impaired intracranial homeostasis. As orthostatic headache can have multiple causes, the term “head and/or neck pain attributed to orthostatic (postural) hypotension” should be replaced with a more inclusive term.

Rapid, Dose-Dependent Enhancement of Cerebral Blood Flow by transcranial AC Stimulation in Mouse

BackgroundTranscranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses. ObjectiveWe performed in vivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation. MethodsWe performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation dose–response function between intracranial electric field and cerebral blood flow. ResultsStimulation at electric field amplitudes of 5–20 mV/mm at 10–20 Hz rapidly increased cerebral blood flow (within 100 ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimulation dose and peak blood flow increase. Neither afterdischarges nor spreading depression occurred from this level of stimulation. ConclusionsExtracranial stimulation amplitudes sufficient to evoke reliable blood flow changes require electric field strengths higher than what is tolerable in unanesthetized humans (<1 mV/mm), but less than electroconvulsive therapy levels (>40 mV/mm). However, anesthesia effects, spontaneous blood flow fluctuations, and sampling error may accentuate the apparent field strength needed for enhanced blood flow. The translation to a human dose–response function to augment cerebral blood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.

Rude mechanicals in brain haemodynamics: non-neural actors that influence blood flow.

Fluctuations in blood oxygenation and flow are widely used to infer brain activity during resting-state functional magnetic resonance imaging (fMRI). However, there are strong systemic and vascular contributions to resting-state signals that are unrelated to ongoing neural activity. Importantly, these non-neural contributions to haemodynamic signals (or 'rude mechanicals') can be as large as or larger than the neurally evoked components. Here, we review the two broad classes of drivers of these signals. One is systemic and is tied to fluctuations in external drivers such as heart rate and breathing, and the robust autoregulatory mechanisms that try to maintain a constant milieu in the brain. The other class comprises local, active fluctuations that appear to be intrinsic to vascular tissue and are likely similar to active local fluctuations seen in vasculature all over the body. In this review, we describe these non-neural fluctuations and some of the tools developed to correct for them when interpreting fMRI recordings. However, we also emphasize the links between these vascular fluctuations and brain physiology and point to ways in which fMRI measurements can be used to exploit such links to gain valuable information about neurovascular health and about internal brain states. This article is part of the theme issue 'Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity'.

Morphology and Function of Myocardium and Skin Microcirculation 24 Hours after Clozapine Poisoning

Aim of the study: to evaluate the effect of sublethal dose of clozapine on the rat cardiovascular system 24 hours after administration of the drug.Materials and methods. The experiments were carried out on 17 male Wistar rats weighing 220-270 g. Under general anesthesia with sevoflurane, the animals of Group I were enterally given 0.9% NaCl solution, Group II animals received clozapine in a dose of 150 mg/kg diluted in 2.0 ml of NaCl solution 0.9%, Group III animals were given clozapine in a dose of 150 mg/kg diluted in 2.0 ml of 40% ethanol. Blood pressure (BP), heart rate (HR), skin microcirculation using laser Doppler flowmetry (LDF), NADH and FAD+ fluorescence were estimated 24 hours after the drug administration. After euthanasia, autopsy with sampling of internal organs for morphological study was done. Then paraffin heart sections with subsequent H&amp;E staining were made, which were studied using the Nikon Eclipse Ni-U light microscope.Results. Spectral analysis of local skin blood flow fluctuations showed that clozapine reduced Amax and amplitude in all frequency ranges of active microcirculation regulatory system in comparison with the controls. No differences in blood gases and acid-base status were seen between the groups of animals 24 hours after administration of the drugs. However, the animals from clozapine groups (II and III) had lower hemoglobin and hematocrit than in the control group.Histological examination of rat hearts in groups II and III revealed congested venules, haemorrhages by dia-pedeses, perivascular and interstitial edema. The signs of blood stasis and marginalization of granulocytes were noted in the vascular lumen. Irregular staining of myocardium due to cardiomyocytes with hypereosinophilic and occasionally homogeneous cytoplasm, fragmentation and deformations of cardiac cells were revealed. Car-diomyocytic nuclei were polymorphic and irregularly stained, and perinuclear edema was observed.Conclusions. The results of the study demonstrate the toxic effect of clozapine manifesting as progressive myocardial alteration and disordered central and peripheral circulation. However, control of bradycardia, restored skin perfusion and metabolic improvement (diagnosed by NADH fluorescence and blood acid-base status) after 24 hours may be due to the activation of compensatory mechanisms, particularly through changes in neurogenic and humoral regulation of homeostasis.

Synchronous Changes in Microcirculation Parameters of the Upper Limbs in Asymmetric Physical Loads

This is the first study on synchronous changes in microcirculation in the symmetrical organs of humans during asymmetric physical loads of the upper limbs. The study was conducted in healthy volunteers by the method of laser Doppler flowmetry (LDF). LDF signal transducers were fixed symmetrically on the lower parts of the right and left shoulders (3 cm above the elbow bend). Physical loads included the left or right arm swings in standing position for 1 min. Measurements were made in three states: (1) initial state, (2) immediately after physical activity, and (3) 5 min after loads. The changes in the mean perfusion value and the components of amplitude-frequency spectrum of blood flow fluctuations (myogenic, neurogenic, respiratory, and cardiac) were evaluated in both sides of the body. We observed the asymmetry of changes in microcirculation parameters after physical loads. It is shown that both left and right swings change the microcirculation parameters of both the left and right sides, and the changes on the left are more pronounced than on the right. A nonlinear relationship was observed between the changes in microcirculation parameters of symmetrical areas of paired organs and heart rate. Our data illustrate the specific regulation patterns of microcirculation blood flow in paired organs, which is associated with functional asymmetry. The physiological mechanisms of this asymmetry require further experimental and clinical research.

A preliminary study of spinal cord blood flow during PVCR with spinal column shortening: A prospective clinic study in severe rigid scoliokyphosis patients.

Posterior vertebral column resection (PVCR) was the most powerful technique for treating severe rigid spinal deformity, but it has been plagued with high neurologic deficits risk. The fluctuations of spinal cord blood flow (SCBF) play an important role in secondary spinal cord injury during deformity correction surgery.The objective of this study was to first provide the characteristic of SCBF during PVCR with spinal column shortening in severe rigid spinal deformity.Severe rigid scoliokyphosis patients received PVCR above L1 level were included in this prospective study. Patients with simple kyphosis, intraspinal pathology and any degree of neurologic deficits were excluded. The deformity correction was based on spinal column shortening over the resected gap during PVCR. Laser Doppler flowmetry was used to monitor the SCBF at different surgical stages.There were 12 severe rigid scoliokyphosis patients in the study. The baseline SCBF was 316 ± 86 perfusion unite (PU), and the SCBF decreased to 228 ± 68 PU after VCR (P = .008). The SCBF increased to 296 ± 102 PU after the middle shortening and correction which has a 121% increased comparison to the SCBF after VCR (P = .02). The SCBF will slightly decrease to 271 ± 65 PU at final fixation. The postoperative neural physical examination of all patients was negative, and the MEP and SSEP of all patients did not reach the alarm value during surgery.These results indicate that PVCR is accompanied by a change in SCBF, a proper spinal cord shortening can protect the SCBF and can prevent a secondary spinal cord injury during the surgery.