Modulation Of Blood Flow Research Articles

Transcranial Magnetic Stimulation Alleviates Levodopa-Induced Dyskinesia in Parkinson's Disease and the Related Mechanisms: A Mini-Review.

After long-term use of levodopa, Parkinson's patients almost inevitably develop dyskinesia, a kind of drug side effect manifesting as uncontrollable choreic movements and dystonia, which could be crippling yet have limited therapeutic options. Transcranial magnetic stimulation is the most widely studied non-invasive neuromodulation technology to treat levodopa-induced dyskinesia. Many studies have shown that transcranial magnetic stimulation has beneficial effects on levodopa-induced dyskinesia and is patient-tolerable, barely with reported adverse effects. Changes in brain connectivity, neuroplasticity, neurotransmitter, neurorestoration, and blood flow modulation could play crucial roles in the efficacy of transcranial magnetic stimulation for levodopa-induced dyskinesia. The appearance of new modes and application for emerging targets are possible solutions for transcranial magnetic stimulation to achieve sustained efficacy. Since the sample size in all available studies is small, more randomized double-blind controlled studies are needed to elucidate the specific treatment mechanisms and optimize treatment parameters.

Edward F. Adolph Distinguished Lecture. It's more than skin deep: thermoregulatory and cardiovascular consequences of severe burn injuries in humans.

Each year, within the United States, tens of thousands of individuals are hospitalized for burn-related injuries. The treatment of deep burns often involves skin grafts to accelerate healing and reduce the risk of infection. The grafting procedure results in a physical disruption between the injured and subsequently debrided host site and the skin graft placed on top of that site. Both neural and vascular connections must occur between the host site and the graft for neural modulation of skin blood flow to take place. Furthermore, evaporative cooling from such burn injured areas is effectively absent, leading to greatly impaired thermoregulatory responses in individuals with large portions of their body surface area burned. Hospitalization following a burn injury can last weeks to months, with cardiovascular and metabolic consequences of such injuries having the potential to adversely affect the burn survivor for years postdischarge. With that background, the objectives of this article are to discuss 1) our current understanding of the physiology and associated consequences of skin grafting, 2) the effects of skin grafts on efferent thermoregulatory responses and the associated consequences pertaining to whole body thermoregulation, 3) approaches that may reduce the risk of excessive hyperthermia in burn survivors, 4) the long-term cardiovascular consequences of burn injuries, and 5) the extent to which burn survivors can "normalize" otherwise compromised cardiovascular responses. Our primary objective is to guide the reader toward an understanding that severe burn injuries result in significant physiological consequences that can persist for years after the injury.

Modulation of pulse travel and blood flow during cuff inflation- An experimental case study.

The blood pressure (BP) cuff can be used to modulate blood flow and propagation of pressure pulse along the artery. In our previous work, we researched methods to adapt cuff modulation techniques for pulse transit time vs. BP calibration and for measurement of other hemodynamic indices of potential interest to critical care, such as arterial compliance. A model characterized the response of the vasculature located directly under the cuff, but assumed that no significant changes occur in the distal vasculature.This study has been tailored to gain insights into the response of distal BP and pulse transit time to cuff inflation. Invasive BP data collected downstream from the cuff demonstrates that highly dynamic processes occur in the distal arm during cuff inflation. Mean arterial pressure increases in the distal artery by up to 20 mmHg, leading to a decrease in pulse transit time of up to 20 ms. Clinical Relevance: Such significant changes need to be taken into account in order to improve non-invasive BP estimations and to enable inference of other hemodynamic parameters from vasculature response to cuff inflation. A simple model is developed in order to reproduce the observed behaviors. The lumped-parameter model demonstrates opportunities for cuff modulation measurements which can reveal information on parameters such as systemic resistance, distal arterial, venous compliances and artery-vein interaction.

Effects of GV14 Acupuncture on Cerebral Blood Flow Velocity in the Basilar and Middle Cerebral Arteries and CO2 Reactivity during Hypercapnia in Normal Individuals.

The Governing Vessel 14 (GV14) (Dazhui) is one of the acupuncture points referred to as “seven acupoints for stroke.” Nevertheless, there is a scarcity of research on the effects of acupuncture treatment at GV14. This study investigated the effects of acupuncture at GV14 on cerebral blood flow (CBF), especially that in the basilar artery (BA) and the middle cerebral arteries (MCA). Sixteen healthy men aged 20 to 29 years were enrolled in this study. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The following were assessed: closed circuit rebreathing- (CCR-) induced carbon dioxide (CO2) reactivity, modified blood flow velocity at 40 mmHg (CV40) on BA and MCAs, blood pressure (BP), and heart rate (HR). Observed results were obtained after comparison with the baseline evaluation. Statistically significant elevations in CO2 reactivity were recorded in the BA (3.28 to 4.70, p < 0.001) and MCAs (right: 3.81 to 5.25, p=0.001; left: 3.84 to 5.12, p=0.005) after acupuncture at GV14. The CV40 increased statistically significantly only in the BA (45.49 to 50.41, p=0.003). No change was observed in BP (106.83 to 107.08 (mmHg), p=0.335) and HR (77 to 75 (bpm), p=0.431). Acupuncture at GV14 improved CBF velocity. These results could be explained by the regulation of endothelium-dependent vessel dilation effected by acupuncture. This trial is registered with Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0004787).

Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4).

Multiple layers of vascular smooth muscle cells (vSMCs) are present in blood vessels forming the media of the vessel wall. vSMCs provide a vessel wall structure, enabling it to contract and relax, thus modulating blood flow. They also play a crucial role in the development of vascular diseases, such as atherosclerosis and aortic aneurysm formation. vSMCs display a remarkable high degree of plasticity. At present, the number of different vSMC phenotypes has only partially been characterized. By mapping vSMC phenotypes in detail and identifying triggers for phenotype switching, the relevance of the different phenotypes in vascular disease may be identified. Up until recently, vSMCs were classified as either contractile or dedifferentiated (ie, synthetic). However, single-cell RNA sequencing studies revealed such dedifferentiated arterial vSMCs to be highly diverse. Currently, no consensus exist about the number of vSMC phenotypes. Therefore, we reviewed the data from relevant single-cell RNA sequencing studies, and classified a total of 6 vSMC phenotypes. The central dedifferentiated vSMC type that we classified is the mesenchymal-like phenotype. Mesenchymal-like vSMCs subsequently seem to differentiate into fibroblast-like, macrophage-like, osteogenic-like, and adipocyte-like vSMCs, which contribute differentially to vascular disease. This phenotype switching between vSMCs requires the transcription factor KLF4 (Krüppel-like factor 4). Here, we performed an integrated analysis of the data about the recently identified vSMC phenotypes, their associated gene expression profiles, and previous vSMC knowledge to better understand the role of vSMC phenotype transitions in vascular pathology.

Effect of liraglutide dose on efficacy of correcting microcirculatory disorders in absolute insulin deficiency of albino rats

The objective was to study the dose-dependent effects of glucagon-like peptide-1 receptor agonist, liraglutide, on microcirculation in white rats under the alloxan-induced insulin deficiency. Materials and Methods. Our study was carried out on 70 white rats, divided into four groups: 20 intact control animals; 20 animals of the comparison group with alloxan-induced diabetes; 10 animals with insulin deficiency, injected with liraglutide at a dose of 0.2 mg/kg per day (treatment group No. 1); and 20 animals with insulin deficiency treated with liraglutide at a dose of 0.4 mg/kg per day (treatment group No. 2). Diabetic status, skin perfusion of the posterior limb and mechanisms of blood flow modulation were assessed in all groups of animals. Results. It was established that administering liraglutide at a dose of 0.4 mg/kg per day allowed achieving complete normalization of carbohydrate metabolism in rats with alloxan-induced insulin deficiency, thereby more effectively improving the state of microcirculation, compared with a dose of 0.2 mg/kg per day. Conclusion. The efficacy of correcting the microcirculatory disorders with liraglutide correlates with correcting the carbohydrate metabolism in rats with insulin deficiency and depends on liraglutide dose. The dose-dependent effect is achieved by the endothelial mechanism of flow modulation in microcirculation. However, the restoration of the vascular tone neurogenic component is independent of liraglutide dose.

Modulation of Pulse Propagation and Blood Flow via Cuff Inflation-New Distal Insights.

In standard critical care practice, cuff sphygmomanometry is widely used for intermittent blood pressure (BP) measurements. However, cuff devices offer ample possibility of modulating blood flow and pulse propagation along the artery. We explore underutilized arrangements of sensors involving cuff devices which could be of use in critical care to reveal additional information on compensatory mechanisms. In our previous work, we analyzed the response of the vasculature to occlusion perturbations by means of observations obtained non-invasively. In this study, our aim is to (1) acquire additional insights by means of invasive measurements and (2) based on these insights, further develop cuff-based measurement strategies. Invasive BP experimental data is collected downstream from the cuff in two patients monitored in the OR. It is found that highly dynamic processes occur in the distal arm during cuff inflation. Mean arterial pressure increases in the distal artery by 20 mmHg, leading to a decrease in pulse transit time by 20 ms. Previous characterizations neglected such distal vasculature effects. A model is developed to reproduce the observed behaviors and to provide a possible explanation of the factors that influence the distal arm mechanisms. We apply the new findings to further develop measurement strategies aimed at acquiring information on pulse arrival time vs. BP calibration, artery compliance, peripheral resistance, artery-vein interaction.

Clinical Applications and Factors Involved in Validating Thermal Windows Used in Infrared Thermography in Cattle and River Buffalo to Assess Health and Productivity.

Simple SummaryInfrared thermography is a clinically useful method for detecting physiopathological alterations in animals through microvascular changes. It has been adapted for applications with large species, as a support tool in evaluating animal welfare, and can also contribute to productive and reproductive evaluations. This review discusses the thermal windows currently in use and characterizes their differences and limitations as resources for early detection and diagnosis in cattle and river buffaloes.Infrared thermography (IRT) is a non-ionizing, non-invasive technique that permits evaluating the comfort levels of animals, a topic of concern due to the growing interest in determining the state of health and welfare of production animals. The operating principle of IRT is detecting the heat irradiated in anatomical regions characterized by a high density of near-surface blood vessels that can regulate temperature gain or loss from/to the environment by modifying blood flow. This is essential for understanding the various vascular thermoregulation mechanisms of different species, such as rodents and ruminants’ tails. The usefulness of ocular, nasal, and vulvar thermal windows in the orbital (regio orbitalis), nasal (regio nasalis), and urogenital (regio urogenitalis) regions, respectively, has been demonstrated in cattle. However, recent evidence for the river buffalo has detected discrepancies in the data gathered from distinct thermal regions in these large ruminants, suggesting a limited sensitivity and specificity when used with this species due to various factors: the presence of hair, ambient temperature, and anatomical features, such as skin thickness and variations in blood supplies to different regions. In this review, a literature search was conducted in Scopus, Web of Science, ScienceDirect, and PubMed, using keyword combinations that included “infrared thermography”, “water buffalo”, “river buffalo” “thermoregulation”, “microvascular changes”, “lacrimal caruncle”, “udder”, “mastitis”, and “nostril”. We discuss recent findings on four thermal windows—the orbital and nasal regions, mammary gland in the udder region (regio uberis), and vulvar in the urogenital region (regio urogenitalis)—to elucidate the factors that modulate and intervene in validating thermal windows and interpreting the information they provide, as it relates to the clinical usefulness of IRT for cattle (Bos) and the river buffalo (Bubalus bubalis).

Eye-Neck Integrated Ultrasound in Idiopathic Intracranial Hypertension and Cerebral Venous Sinus Thrombosis.

Background: The clinical presentation of cerebral venous sinus thrombosis (CVST) overlaps with that of idiopathic intracranial hypertension (IIH), but no screening tool exists. We investigated the role of eye-neck integrated ultrasound in the diagnosis and differentiation of IIH and CVST.Methods: Twenty IIH patients, 30 CVST patients, and 40 healthy controls were retrospectively analyzed. The ultrasonographic optic nerve sheath diameter (ONSD) and hemodynamic characteristics of the internal jugular veins (IJVs) were recorded. The cerebrospinal fluid opening pressure was measured after ultrasonic examination.Results: The ONSD was significantly larger in IIH patients than in controls (4.71 ± 0.41 vs. 3.93 ± 0.24 mm, p < 0.001). The ONSD cut-off for IIH diagnosis was 4.25 mm (AUC = 0.978; 95% CI: 0.95–1.0, p < 0.001, sensitivity: 90%, specificity: 93%). In the CVST group, 22 (73.3%) patients had elevated intracranial pressure (ICP); the mean ONSD was significantly higher in patients with increased ICP than in those without (4.43 ± 0.33 vs. 3.95 ± 0.17 mm, p < 0.001). The mean blood flow volume (BFV) was significantly reduced in CVST patients (425.17 ± 349.83 mL/min) compared to that in controls (680.37 ± 233.03 mL/min, p < 0.001) and IIH patients (617.67 ± 282.96 mL/min, p = 0.008). The optimal BFV cut-off for predicting CVST was 527.28 mL/min (AUC = 0.804, 95% CI: 0.68–0.93, p < 0.001, sensitivity: 80%, specificity: 78%). The velocity of the unilateral IJVs-J3 segment decreased or remained constant during deep inspiration (abnormal respiratory modulate blood flow test, ARMT) in 32.5% of controls, with no bilateral ARMT. The prevalence of bilateral ARMT was 25% in IIH patients (χ2 = 12.9, p = 0.005) and 27% in CVST patients (χ2 = 17.6, p = 0.001).Conclusion: Eye-neck integrated ultrasound is an easily available bedside technique to assess ICP and hemodynamic characteristics of IJVs. ONSD measurement can identify patients with increased ICP, and reduced IJV BFV may aid the differentiation of CVST and IIH.

Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit.

The neurovascular unit (NVU) of the brain is composed of multiple cell types that act synergistically to modify blood flow to locally match the energy demand of neural activity, as well as to maintain the integrity of the blood-brain barrier (BBB). It is becoming increasingly recognized that the functional specialization, as well as the cellular composition of the NVU varies spatially. This heterogeneity is encountered as variations in vascular and perivascular cells along the arteriole-capillary-venule axis, as well as through differences in NVU composition throughout anatomical regions of the brain. Given the wide variations in metabolic demands between brain regions, especially those of gray vs. white matter, the spatial heterogeneity of the NVU is critical to brain function. Here we review recent evidence demonstrating regional specialization of the NVU between brain regions, by focusing on the heterogeneity of its individual cellular components and briefly discussing novel approaches to investigate NVU diversity.

Percutaneous Trigeminal Nerve Stimulation Induces Cerebral Vasodilation in a Dose-Dependent Manner.

The trigeminal nerve directly innervates key vascular structures both centrally and peripherally. Centrally, it is known to innervate the brainstem and cavernous sinus, whereas peripherally the trigemino-cerebrovascular network innervates the majority of the cerebral vasculature. Upon stimulation, it permits direct modulation of cerebral blood flow (CBF), making the trigeminal nerve a promising target for the management of cerebral vasospasm. However, trigeminally mediated cerebral vasodilation has not been applied to the treatment of vasospasm. To determine the effect of percutaneous electrical stimulation of the infraorbital branch of the trigeminal nerve (pTNS) on the cerebral vasculature. In order to determine the stimulus-response function of pTNS on cerebral vasodilation, CBF, arterial blood pressure, cerebrovascular resistance, intracranial pressure, cerebral perfusion pressure, cerebrospinal fluid calcitonin gene-related peptide (CGRP) concentrations, and the diameter of cerebral vessels were measured in healthy and subarachnoid hemorrhage (SAH) rats. The present study demonstrates, for the first time, that pTNS increases brain CGRP concentrations in a dose-dependent manner, thereby producing controllable cerebral vasodilation. This vasodilatory response appears to be independent of the pressor response induced by pTNS, as it is maintained even after transection of the spinal cord at the C5-C6 level and shown to be confined to the infraorbital nerve by administration of lidocaine or destroying it. Furthermore, such pTNS-induced vasodilatory response of cerebral vessels is retained after SAH-induced vasospasm. Our study demonstrates that pTNS is a promising vasodilator and increases CBF, cerebral perfusion, and CGRP concentration both in normal and vasoconstrictive conditions.

Restriction of Atrial Septal Defect Leads to Growth of Hypoplastic Ventricle in Patients with Borderline Right or Left Heart

Patients with borderline hypoplastic right or left ventricle and VSD may be candidates for either single ventricle palliation or staged ventricular recruitment (SVR) followed by eventual biventricular conversion. Components of SVR include restriction of atrial septal defects (ASD) without ventricular septal defects (VSD) closure and addition of accessory pulmonary blood flow. This study evaluated the impact of ASD restriction on ventricular growth and function. We retrospectively reviewed patients with borderline ventricular hypoplasia and VSD who underwent a staged ventricular recruitment (SVR) procedure from 2012 to June 2019. Pre- and post-recruitment MRI and echocardiogram data were compared and analyzed. We excluded cases in which we intentionally restricted VSD with simultaneous ASD restriction. Forty-six patients (41 with right-dominant ventricle, 25 with risk factors for Fontan procedure) underwent SVR at a median age of 15.1 months' (interquartile range (IQR), 7.2-37.2 months'). The median indexed ventricular end-diastolic volume, end-systolic volume, and stroke volume according to cardiac MRI significantly increased at median 11.0 months' (IQR:7.8~14.1 months') after recruitment. Among them, except 2 operative mortalities after SVR, 26 patients underwent bi-ventricular repair (56.5% including one and a half ventricle repair) at a median of 8.0 months' (IQR: 6.2-12.2 months') after recruitment. Fifteen patients await biventricular completion, and 3 patients underwent single ventricle palliation. Pulmonary blood flow (Qp) tended to increase after recruitment regardless of type of pulmonary blood flow modification without statistical significance. Six patients died at a median duration of 6.5 months' (IQR: 2.9-11.7) after SVR; 3 patients died after biventricular completion, 2 after recruitment, and 1 after returning to single ventricle palliation. All of them were considered poor Fontan candidates due to severe atrioventricular valve regurgitation, pulmonary hypertension, pulmonary vein stenosis, or airway stenosis. Restriction of the atrial septum leads to the growth of hypoplastic ventricle in patients with ventricular septal defects who undergo SVR regardless of the preoperative characteristics, and eventual biventricular repair can be performed in a subgroup of these patients. Future work is necessary to optimize timing of SVR and method of accessory pulmonary blood flow.

Real-Time Multifrequency MR Elastography of the Human Brain Reveals Rapid Changes in Viscoelasticity in Response to the Valsalva Maneuver.

Modulation of cerebral blood flow and vascular compliance plays an important role in the regulation of intracranial pressure (ICP) and also influences the viscoelastic properties of brain tissue. Therefore, magnetic resonance elastography (MRE), the gold standard for measuring in vivo viscoelasticity of brain tissue, is potentially sensitive to cerebral autoregulation. In this study, we developed a multifrequency MMRE technique that provides serial maps of viscoelasticity at a frame rate of nearly 6 Hz without gating, i.e., in quasi-real time (rt-MMRE). This novel method was used to monitor rapid changes in the viscoelastic properties of the brains of 17 volunteers performing the Valsalva maneuver (VM). rt-MMRE continuously sampled externally induced vibrations comprising three frequencies of 30.03, 30.91, and 31.8 Hz were over 90 s using a steady-state, spiral-readout gradient-echo sequence. Data were processed by multifrequency dual elasto-visco (MDEV) inversion to generate maps of magnitude shear modulus | G∗| (stiffness) and loss angle φ at a frame rate of 5.4 Hz. As controls, the volunteers were examined to study the effects of breath-hold following deep inspiration and breath-hold following expiration. We observed that | G∗| increased while φ decreased due to VM and, less markedly, due to breath-hold in inspiration. Group mean VM values showed an early overshoot of | G∗| 2.4 ± 1.2 s after the onset of the maneuver with peak values of 6.7 ± 4.1% above baseline, followed by a continuous increase in stiffness during VM. A second overshoot of | G∗| occurred 5.5 ± 2.0 s after the end of VM with peak values of 7.4 ± 2.8% above baseline, followed by 25-s sustained recovery until the end of image acquisition. φ was constantly reduced by approximately 2% during the entire VM without noticeable peak values. This is the first report of viscoelasticity changes in brain tissue induced by physiological maneuvers known to alter ICP and detected by clinically applicable rt-MMRE. Our results show that apnea and VM slightly alter brain properties toward a more rigid-solid behavior. Overshooting stiffening reactions seconds after onset and end of VM reveal rapid autoregulatory processes of brain tissue viscoelasticity.

Glucagon-like peptide-1 (GLP-1) receptor activation dilates cerebral arterioles, increases cerebral blood flow, and mediates remote (pre)conditioning neuroprotection against ischaemic stroke

Stroke remains one of the most common causes of death and disability worldwide. Several preclinical studies demonstrated that the brain can be effectively protected against ischaemic stroke by two seemingly distinct treatments: remote ischaemic conditioning (RIC), involving cycles of ischaemia/reperfusion applied to a peripheral organ or tissue, or by systemic administration of glucagon-like-peptide-1 (GLP-1) receptor (GLP-1R) agonists. The mechanisms underlying RIC- and GLP-1-induced neuroprotection are not completely understood. In this study, we tested the hypothesis that GLP-1 mediates neuroprotection induced by RIC and investigated the effect of GLP-1R activation on cerebral blood vessels, as a potential mechanism of GLP-1-induced protection against ischaemic stroke. A rat model of ischaemic stroke (90 min of middle cerebral artery occlusion followed by 24-h reperfusion) was used. RIC was induced by 4 cycles of 5 min left hind limb ischaemia interleaved with 5-min reperfusion periods. RIC markedly (by ~ 80%) reduced the cerebral infarct size and improved the neurological score. The neuroprotection established by RIC was abolished by systemic blockade of GLP-1R with a specific antagonist Exendin(9–39). In the cerebral cortex of GLP-1R reporter mice, ~ 70% of cortical arterioles displayed GLP-1R expression. In acute brain slices of the rat cerebral cortex, activation of GLP-1R with an agonist Exendin-4 had a strong dilatory effect on cortical arterioles and effectively reversed arteriolar constrictions induced by metabolite lactate or oxygen and glucose deprivation, as an ex vivo model of ischaemic stroke. In anaesthetised rats, Exendin-4 induced lasting increases in brain tissue PO2, indicative of increased cerebral blood flow. These results demonstrate that neuroprotection against ischaemic stroke established by remote ischaemic conditioning is mediated by a mechanism involving GLP-1R signalling. Potent dilatory effect of GLP-1R activation on cortical arterioles suggests that the neuroprotection in this model is mediated via modulation of cerebral blood flow and improved brain perfusion.

Dopaminergic modulation of regional cerebral blood flow: An arterial spin labelling study of genetic and pharmacological manipulation of COMT activity

Dopamine has direct and complex vasoactive effects on cerebral circulation. Catechol-O-methyltransferase (COMT) regulates cortical dopamine, and its activity can be influenced both genetically and pharmacologically. COMT activity influences the functional connectivity of the PFC at rest, as well as its activity during task performance, determined using blood oxygen level-dependent (BOLD) fMRI. However, its effects on cerebral perfusion have been relatively unexplored. Here, 76 healthy males, homozygous for the functional COMT Val158Met polymorphism, were administered either the COMT inhibitor tolcapone or placebo in a double-blind, randomised design. We then assessed regional cerebral blood flow at rest using pulsed arterial spin labelling. Perfusion was affected by both genotype and drug. COMT genotype affected frontal regions (Val158 > Met158), whilst tolcapone influenced parietal and temporal regions (placebo > tolcapone). There was no genotype by drug interaction. Our data demonstrate that lower COMT activity is associated with lower cerebral blood flow, although the regions affected differ between those affected by genotype compared with those altered by acute pharmacological inhibition. The results extend the evidence for dopaminergic modulation of cerebral blood flow. Our findings also highlight the importance of considering vascular effects in functional neuroimaging studies, and of exercising caution in ascribing group differences in BOLD signal solely to altered neuronal activity if information about regional perfusion is not available.

Brain capillary pericytes exert a substantial but slow influence on blood flow.

The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and pre-capillary arterioles. This slow vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically-induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.

Durable Continuous-Flow Mechanical Circulatory Support: State of the Art

Implantable mechanical circulatory support (MCS) systems for ventricular assist device (VAD) therapy have emerged as an important strategy due to a shortage of donor organs for heart transplantation. A growing number of patients are receiving permanent assist devices, while fewer are undergoing heart transplantation (Htx). Continuous-flow (CF) pumps, as devices that can be permanently implanted, show promise for the treatment of both young and old patients with heart failure (HF). Further improvement of these devices will decrease adverse events, enable pulse modulation of continuous blood flow, and improve automatic remote monitoring. Ease of use for patients could also be improved. We herein report on the current state of the art regarding implantable CF pumps for use as MCS systems in the treatment of advanced refractory HF.

Impact of High Temperature on Oocytes and Embryos: A Review

High temperature is one of the leading factors for decline reproductive performance in livestock and other species as a result of heat stress causing severe economic losses. The embryonic death causes due to heat stress is having multifactorial mechanism in live animal. Heat stress could influence reproductive physiology through modulating blood flow to the reproductive tract, ovarian steroid concentrations and patterns of follicular development. It is difficult for embryos to survive in the increase an oviductal and uterine temperature which is coincident with heat stress. In vitro culture of embryos at high temperatures has been reported to affect embryonic development. Similarly, increased in vitroculture temperatures can compromise oocyte activity and reduce fertilization rate. Studies have demonstrated that there were lethal effects of heat shock on in vitro cultured embryos of cattle at 41.0 – 43.0°C. However, these experimental temperatures are higher than those generally experienced by heat-stressed cows which ultimately reduced their fertility. Furthermore, a lot of research have been conducted in livestock species all indicating that exposure to high temperature is detrimental to oocytes and embryonic developmental processes as it leads to cell damage and may interfere with oocyte maturation, and fertilization process. It concludes that the longer exposure of oocytes and embryos to high temperatures causes more damage to oocytes and embryos.

Placental Corticotrophin-Releasing Hormone is a Modulator of Fetal Liver Blood Perfusion.

Variation in fetal liver blood flow influences fetal growth and postnatal body composition. Placental corticotrophin-releasing hormone has been implicated as a key mediator of placental-fetal perfusion. To determine whether circulating levels of placental corticotrophin-releasing hormone across gestation are associated with variations in fetal liver blood flow. Prospective cohort study. Fetal ultrasonography was performed at 30 weeks' gestation to characterize fetal liver blood flow (quantified by subtracting ductus venosus flow from umbilical vein flow). Placental corticotrophin-releasing hormone was measured in maternal circulation at approximately 12, 20, and 30 weeks' gestation. Multiple regression analysis was used to determine the proportion of variation in fetal liver blood flow explained by placental corticotrophin-releasing hormone. Covariates included maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and fetal sex. A total of 79 uncomplicated singleton pregnancies were analyzed. Fetal liver blood flow was 68.4 ± 36.0 mL/min (mean ± SD). Placental corticotrophin-releasing hormone concentrations at 12, 20, and 30 weeks were 12.5 ± 8.1, 35.7 ± 24.5, and 247.9 ± 167.8 pg/mL, respectively. Placental corticotrophin-releasing hormone at 30 weeks, but not at 12 and 20 weeks, was significantly and positively associated with fetal liver blood flow at 30 weeks (r = 0.319; P = 0.004) and explained 10.4% of the variance in fetal liver blood flow. Placental corticotrophin-releasing hormone in late gestation is a possible modulator of fetal liver blood flow and may constitute a biochemical marker in clinical investigations of fetal growth and body composition.

Microcirculation disorders and structural and functional left ventricular abnormalities in patients with type 1 diabetes complicated by ketoacidosis

Aim. To assess the patterns of microcirculation disorders and its effect on the left ventricular (LV) structure and function in patients with type 1 diabetes (T1D) complicated by diabetic ketoacidosis (DKA).Material and methods. The study included 128 patients with T1D complicated by DKA. Echocardiography was performed according to the standard technique. To study the microcirculation and vascular tone regulation, we used a laser Doppler flowmetry (LDF) using the LAKK-02 machine (Lazma, Russia).Results. In patients with T1D complicated by DKA, there was an increase in thepassive blood flow modulation with a depression of active factors. The most pronounced changes are recorded in 1-5 days of the disease. Along with this, a spectral redistribution in favour of respiratory and cardiac microcirculation ranges was demonstrated. With DKA, the myocardial remodelling is recorded: an increase in left atrial (LA) size by 5,6%, LV end systolic and diastolic dimension and volume by 5,3% and 6,7%, respectively, LV mass by 17,3% and LV mass index by 17,8%. Decreased LV ejection fraction (EF) in comparison with healthy individuals was obtained. Significant unidirectional changes in these parameters were revealed in comparison with the T1D patients without DKA.Conclusion. In patients with T1D complicated by DKA, the microcirculation decreases, as a result of which the adequate tissue supply is limited, vascular resistance and hemodynamic load increases, which leads to LV structural and functional changes.