Blood Flow Hemodynamics Research Articles

Circadian rhythm of brain-derived neurotrophic factor in serum and plasma.

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

Doppler ultrasound compared to shear wave elastography for assessment of liver cirrhosis

BackgroundThe progression of liver fibrosis to cirrhosis is a dynamic process necessitating non-invasive evaluation modalities. This study aims to evaluate the ability of Doppler ultrasound studies (DUS) in defining morphological and hemodynamic blood flow changes in the hepatic vasculature coinciding with advanced liver fibrosis.MethodsA prospective study was conducted on 100 patients with liver cirrhosis (F4). All cases underwent liver stiffness (LS) measurement by shear wave elastography (SWE), along with DUS to evaluate the liver texture, splenic size, hepatic artery resistive index (HARI), portal and splenic vein diameters, portal vein velocity (PVV), and hepatic vein waveform (HVV). All measures were assessed concurrently with a highly qualified single operator.ResultsPatients aged 55.5 ± 10.2 years with male predominance (72%). A highly significant correlation was found between LS by SWE and hepatic parenchymal texture, splenic size, portal vein width, and HVV (monophasic and biphasic) (p < 0.001). There were also high significant positive correlations (p < 0.001) between LS and PVV. However, there was no definitive correlation between LS and HARI, as well as splenic vein diameter.ConclusionThe widely available economic Doppler studies including portal vein velocity and hepatic vein waveform changes could be of substantial diagnostic value to liver cirrhosis.Study designProspective cohort study, employing descriptive and analytical statistics.

Chronic inflammation with microglia senescence at basal forebrain: impact on cholinergic deficit in Alzheimer's brain haemodynamics.

Cholinergic innervation in the brain is involved in modulating neurovascular function including cerebral blood flow haemodynamics in response to neuronal activity. Cholinergic deficit is associated with pathophysiology in Alzheimer's disease, albeit the aetiology remains to be clarified. In the current study, neocortex cerebral blood flow response to acetylcholine was evaluated by Laser-Doppler Flowmetry (LDF) in 3xTgAD Alzheimer's disease model) and wild-type mice of two age groups. The peak of cerebral blood flow to acetylcholine (i.v.) from baseline levels (% ΔrCBF) was higher in young 3xTgAD versus in wild-type mice (48.35; 95% CI:27.03-69.67 versus 22.70; CI:15.5-29.91, P < 0.05); this was reversed in old 3xTgAD mice (21.44; CI:2.52-40.35 versus 23.25; CI:23.25-39). Choline acetyltransferase protein was reduced in neocortex, while cerebrovascular reactivity to acetylcholine was preserved in young 3×TgAD mice. This suggests endogenous acetylcholine deficit and possible cholinergic denervation from selected cholinergic nuclei within the basal forebrain. The early deposition of tauopathy moieties (mutant hTau and pTau181) and its coincidence in cholinergic cell clusters (occasionaly), were observed at the basal forebrain of 3xTgAD mice including substantia innominate, nucleus Basalis of Meynert and nucleus of horizontal limb diagonal band of Broca. A prominent feature was microglia interacting tauopathy and demonstrated a variety of morphology changes particularly when located in proximity to tauopathy. The microglia ramified phenotype was reduced as evaluated by the ramification index and Fractal analysis. Increased microglia senescence, identified as SASP (senescence-associated secretory phenotype), was colocalization with p16Ink4ɑ, a marker of irreversible cell-cycle arrest in old 3xTgAD versus wild-type mice (P = 0.001). The p16Ink4ɑ was also observed in neuronal cells bearing tauopathy within the basal forebrain of 3xTgAD mice. TNF-ɑ, the pro-inflammatory cytokine elevated persistently in microglia (Pearson's correlation coefficient = 0.62) and the loss of cholinergic cells in vulnerable basal forebrain environment, was indicated by image analysis in 3xTgAD mice, which linked to the cholinergic deficits in neocortex rCBF haemodynamics. Our study revealed the early change of CBF haemodynamics to acetylcholine in 3xTgAD model. As a major effector of brain innate immune activation, microglia SASP with age-related disease progression is indicative of immune cell senescence, which contributes to chronic inflammation and cholinergic deficits at the basal forebrain. Targeting neuroinflammation and senescence may mitigate cholinergic pathophysiology in Alzheimer's disease.

Hemodynamic coupling between a primary atherosclerotic plaque and subsequent secondary lesions

Atherosclerosis is one of the most common diseases of the arterial tree, especially in the coronary arteries. Stenoses exceeding 50% area reduction are shown to alternate the downstream coronary flow, and hemodynamics will lead to further atherogenesis. Clinical evidence also confirms that vascular stenoses are not stagnant since they are usually associated with downstream lesions. In this study, it is hypothesized that the formation of secondary plaques, or aneurysms downstream of a primary stenosis, compensates for the abnormal ranges of hemodynamic forces caused by the primary stenosis. An experimental setup captured the hemodynamics of non-Newtonian blood flow in three-dimensional (3D) printed phantoms of coronary arteries with various sequences of lesions. Then, based on the collected data, in silico models of these lesions were simulated using computational fluid dynamics. For the proposed cases, time-averaged wall shear stress, velocity profile, oscillatory shear index, and relative residence time were extracted at the plaque side and the plaque front walls and compared to the reference model with only the primary plaque. The secondary plaque postulated the abnormal hemodynamic conditions to its downstream, which implies endothelial activation and onset of further pathologic events. However, the secondary aneurysm restored flow conditions to normal after its distal shoulder, preventing more damage to the endothelium. Examined angiograms of patients with developed atherosclerotic lesions unveiled that a sequence of plaques is formed over time, and most interestingly, the series stopped after the formation of an aneurysm.

Multifaceted simulation: Finite volume and finite element modeling of blood flow in multiple stenosed arteries

Cardiovascular illnesses are a primary global health concern because they are frequently brought on by arterial stenosis. The complicated hemodynamics of blood flow via elliptically shaped arteries with numerous stenotic lesions along their top and bottom walls are examined in this paper. Carreau fluid model is used with Navier–Stokes equations in this study. The complete comparative study is done by using the Finite Element and Finite Volume Methods. This study uses commercial software to examine blood flow velocity, pressure and temperature distributions under various physiological situations at Reynolds number 30. Our results illuminate the interaction between flow dynamics, stenosis characteristics, and arterial geometry. The novelty of the work is to investigate how stenosis size, shape, and location affect pressure gradients, and flow disturbances. These observations provide helpful direction for understanding disease progression, designing treatments, and possibly new stent designs. The future direction of this research may involve further exploration of the interplay between hemodynamics and arterial stenosis by incorporating advanced computational models. Additionally, studies focusing on in vivo validation and clinical applications could enhance the translational impact of the findings. Collaborations between researchers, clinicians, and engineers may pave the way for personalized treatment strategies and innovations in cardiovascular care based on a deeper understanding of the intricate dynamics within diseased arteries.

Numerical Analysis of Stenosis Geometry and Stent Effects on the Hemodynamics of Blood Flow Through the Artery

Numerical Analysis of Stenosis Geometry and Stent Effects on the Hemodynamics of Blood Flow Through the Artery

Nanoparticle aggregation and electro-osmotic propulsion in peristaltic transport of third-grade nanofluids through porous tube

In the modern era, the utilization of electro-kinetic-driven microfluidic pumping procedures spans various biomedical and physiological domains. The present study introduces a mathematical framework for characterizing the hemodynamics of peristaltic blood flow within a porous tube infused with ZrO2 nanoparticles. This model delves into the interactions between buoyancy, electro-osmotic forces, and aggregated nanoparticles to discern their influence on blood flow. We employ a third-grade fluid model to elucidate the rheological behavior of the pseudoplastic fluid which refers to its response to applied shear stress, specifically the relationship between shear rate and viscosity. The collective influence of accommodating heat convection, joule heating and aggregated nanoparticles contributes to the thermal behavior of fluids. The distribution of electric potential within the electric double layer (EDL) is predicted by solving the Poisson–Boltzmann equation. The rescaled equations are simplified using the lubrication and Debye-Hückel models as the underlying frameworks. The novel homotopy perturbation method is employed to obtain solutions for the finalized non-linear partial differential equation. Theoretical assessment of hemodynamic impacts involves plotting graphical configurations for various emerging parameters. As electro-osmotic parameter increase, the bloodstream encounters greater impedance, thereby enhancing the effectiveness of electro-osmotic assistance. Concurrently, elevated convective heat markedly reduces the rate of heat transfer, potentially resulting in a drop in blood temperature. It is important to note that maximum shear stress occurs when the artery is positioned horizontally, underscoring the significant impact of arterial alignment on wall shear stress. Skin friction intensifies with the increasing wall permeability as aggregated nanofluids pass through the arterial conduit. Therefore, aggregation of nanoparticles into the bloodstream yields a broader spectrum of distinctive physiological features. In summary, these findings enable more effective tool and device designs for addressing medication administration challenges and electro-therapies.

Individualized management of chronic periodontitis in patients with orthodontic abnormalities: a clinical case report

Relevance. Chronic periodontitis is a multifactorial disease influenced by a variety of factors. Beyond periodontal pathogens and systemic conditions, important contributing factors include malocclusion, dental misalignment, and tooth loss. These conditions can compromise the tissue blood flow hemodynamics and precipitate occlusal trauma with signs of functional overload. Subsequently, this may intensify the inflammation and degradation of the alveolar bone, often leading to premature tooth loss.Correction of malocclusion is paramount in the effective management of periodontal diseases, requiring orthodontic treatment to resolve malocclusion and mitigate signs of functional overload. This treatment aims to redistribute occlusal forces uniformly, thus creating a conducive environment for successful prosthodontic rehabilitation and promoting optimal personal oral hygiene.Clinical case description. This article outlines a personalized approach to managing periodontal inflammation in individuals with orthodontic anomalies. Patient Z., born in 2002, was diagnosed with moderate severity chronic periodontitis (K05.31), presenting with a Class I molar and canine relationship on both sides, constricted dental arches, individual tooth macrodontia, and retrusion and torsiversion of the incisors. The assessment of the patient's periodontal status and overall health was conducted using standard clinical, radiographic, and laboratory diagnostics, whereas the orthodontic assessment involved anthropometric analysis of dental casts and lateral cephalometric radiographs. The periodontal intervention included foundational non-surgical treatments such as ultrasonic scaling both supra- and subgingivally, biofilm disruption using the Vector Paro system, and specific pharmacotherapy. The orthodontic treatment aimed to widen both dental arches and correct the inclination of the upper and lower incisors, achieving a normal occlusion with fixed orthodontic appliances (Damon Q brackets) in accordance with the treatment plan. The effectiveness of the treatment was measured by examining the improvement in gingival conditions, periodontal parameters, and radiographic evidence before and after the intervention.Conclusion. The research demonstrated that an individualized treatment protocol integrating periodontal and orthodontic care can substantially improve the overall health of the dentofacial complex, masticatory efficiency, and aesthetic aspects.

Haemodynamics of stent-mounted neural interfaces in tapered and deformed blood vessels

The endovascular neural interface provides an appealing minimally invasive alternative to invasive brain electrodes for recording and stimulation. However, stents placed in blood vessels have long been known to affect blood flow (haemodynamics) and lead to neointimal growth within the blood vessel. Both the stent elements (struts and electrodes) and blood vessel wall geometries can affect the mechanical environment on the blood vessel wall, which could lead to unfavourable vascular remodelling after stent placement. With increasing applications of stents and stent-like neural interfaces in venous blood vessels in the brain, it is necessary to understand how stents affect blood flow and tissue growth in veins. We explored the haemodynamics of a stent-mounted neural interface in a blood vessel model. Results indicated that blood vessel deformation and tapering caused a substantial change to the lumen geometry and the haemodynamics. The neointimal proliferation was evaluated in sheep implanted with an endovascular neural interface. Analysis showed a negative correlation with the mean Wall Shear Stress pattern. The results presented here indicate that the optimal stent oversizing ratio must be considered to minimise the haemodynamic impact of stenting.

MRI Investigation of the Association of Left Atrial and Left Atrial Appendage Hemodynamics with Silent Brain Infarction.

Left atrial (LA) myopathy is thought to be associated with silent brain infarctions (SBI) through changes in blood flow hemodynamics leading to thrombogenesis. 4D-flow MRI enables in-vivo hemodynamic quantification in the left atrium (LA) and LA appendage (LAA). To determine whether LA and LAA hemodynamic and volumetric parameters are associated with SBI. Prospective observational study. A single-site cohort of 125 Participants of the multiethnic study of atherosclerosis (MESA), mean age: 72.3 ± 7.2 years, 56 men. 1.5T. Cardiac MRI: Cine balanced steady state free precession (bSSFP) and 4D-flow sequences. Brain MRI: T1- and T2-weighted SE and FLAIR. Presence of SBI was determined from brain MRI by neuroradiologists according to routine diagnostic criteria in all participants without a history of stroke based on the MESA database. Minimum and maximum LA volumes and ejection fraction were calculated from bSSFP data. Blood stasis (% of voxels <10 cm/sec) and peak velocity (cm/sec) in the LA and LAA were assessed by a radiologist using an established 4D-flow workflow. Student's t test, Mann-Whitney U test, one-way ANOVA, chi-square test. Multivariable stepwise logistic regression with automatic forward and backward selection. Significance level P < 0.05. 26 (20.8%) had at least one SBI. After Bonferroni correction, participants with SBI were significantly older and had significantly lower peak velocities in the LAA. In multivariable analyses, age (per 10-years) (odds ratio (OR) = 1.99 (95% confidence interval (CI): 1.30-3.04)) and LAA peak velocity (per cm/sec) (OR = 0.87 (95% CI: 0.81-0.93)) were significantly associated with SBI. Older age and lower LAA peak velocity were associated with SBI in multivariable analyses whereas volumetric-based measures from cardiac MRI or cardiovascular risk factors were not. Cardiac 4D-flow MRI showed potential to serve as a novel imaging marker for SBI. 3 TECHNICAL EFFICACY: Stage 2.

Digital artery flow hemodynamics: An ultrasonographic study

BackgroundThere is a lack of data regarding the baseline hemodynamic blood flow parameters of the wrist and digits. Therefore, we aimed to quantify the digital and radial artery blood flow parameters using ultrasound and assess the influence of patient characteristics on hemodynamics. MethodsWe analyzed ultrasonographic data from 25 patients (50 hands) between October 2019 and December 2021. Variables of interest included dimensions of the radial artery and index finger (IF) ulnar and radial digital arteries at the palmodigital crease and their corresponding flow parameters. We compared variables among men and women and patients with and without diabetes using Wilcoxon Rank Sum test. ResultsOur cohort consisted of 18 women (36 hands) and three participants with diabetes (six hands). The mean diameter of the IF radial digital artery was 7 mm, and that of the ulnar digital artery was 10 mm. The average peak systolic velocity for the radial digital artery was 21.31 cm/sec, and for the ulnar digital artery, it was 30.03 cm/sec. Comparing men and women, the only significant difference found was in the time-averaged mean velocity for the ulnar digital artery (men:5.66 cm/sec vs. women:9.68 cm/sec, P = 0.02) and volume of flow for the ulnar digital artery (men:10.87cc/min vs. women:18.58cc/min, P = 0.03). We found no differences in blood flow parameters comparing participants with and without diabetes. ConclusionThese data provide a baseline measurement of digital flow hemodynamics that can be used in future studies to model vascular flow after replantation.

Computational Fluid Dynamic Simulation of the Cerebral Venous System in Multiple Sclerosis and Control Patients: Are Hemodynamic Variances Evident in Multiple Sclerosis?

An investigation was performed to determine the relevant hemodynamic parameters which could help assess vascular pathology in human diseases. Using these parameters, this study aims to assess if there are any hemodynamic differences in the cerebral veins of multiple sclerosis (MS) patients and controls which could impact the etiology of MS. 40 MS participants and 20 controls were recruited for this study. Magnetic resonance imaging (MRI) was performed to enable 3D geometries of the anatomy and the blood flow rates at the boundaries to be computed. Computational fluid dynamics (CFD) models were created for each participant and simulated using patient-specific boundary conditions. The pressure drop and vascular resistance did not significantly differ between the groups. The internal jugular vein (IJV) cross-sectional area was larger in the MS group (Right IJV: p = 0.04, Left IJV: p = 0.02) and the straight sinus (ST) flow rate was higher in MS across all ages (p = 0.005) compared to controls. Vascular resistance was shown to indicate regions in the cerebral veins which could correspond to increased venous pressure. Conclusion & Significance: This study shows that the pressure and vascular resistance of the cerebral veins are unlikely to be directly related to the etiology of MS. The finding of higher ST flow could correspond to increased inflammation in the deep venous system. Resistance as a measure of vascular pathology shows promise and could be useful to holistically investigate blood flow hemodynamics in a variety of other diseases of the circulatory system.

Influence of Fluid Rheology on Blood Flow Haemodynamics in Patient-Specific Arterial Networks of Varied Complexity – In-Silico Studies

Abstract Results obtained with computational fluid dynamics (CFD) rely on assumptions made during a pre-processing stage, including a mathematical description of a fluid rheology. Up to this date there is no clear answer to several aspects, mainly related to the question of whether and under what conditions blood can be simplified to a Newtonian fluid during CFD analyses. Different research groups present contradictory results, leaving the question unanswered. Therefore, the objective of this research was to perform steady-state and pulsatile blood flow simulations using eight different rheological models in geometries of varying complexity. A qualitative comparison of shear- and viscosity-related parameters showed no meaningful discrepancies, but a quantitative analysis revealed significant differences, especially in the magnitudes of wall shear stress (WSS) and its gradient (WSSG). We suggest that for the large arteries blood should be modelled as a non-Newtonian fluid, whereas for the cerebral vasculature the assumption of blood as a simple Newtonian fluid can be treated as a valid simplification.

Reducing thrombotic risks in video gamers: investigating the benefits of walking and compression sleeves on blood hemodynamics.

With the growing popularity of video gaming, deep vein thromboses are increasingly being reported in gamers. This study aimed to compare the effects of lower leg graduated compression sleeves and a 6-min walking break during prolonged gaming on blood flow and hemodynamics in competitive sport players to help mitigate this risk. Ten healthy gamers (19.6 ± 1.2 yr old; 9 men) consented to participate in this mixed-model crossover design study that consisted of three visits. In visit 1, participants engaged in continuous 2-h video game play wearing no compression (continuous). Visits 2 and 3 involved 2-h play wearing compression sleeves (compression) and 2-h game play interrupted at 1 h by a 6-min walk (walk). Doppler ultrasound measurements of the left popliteal artery were taken at 30, 60, 90, and 120 min, to record vessel diameter, blood flow velocity, and blood flow volume. Participants completed a survey to assess their perception of each approach. There was a significant interaction between conditions for blood flow and blood velocity (P = 0.01, P < 0.001). Post hoc analysis demonstrated a greater decrease in blood flow and blood velocity in the continuous group compared with the walk group at the 90-min mark (P = 0.04, P = 0.01). No differences were found between the compression and walk groups or between the continuous and compression groups (P = 0.42, P = 0.69). No interactions were observed in diameter, mean arterial pressure, or heart rate. This study suggests that incorporating a 6-min walk every 60 min during prolonged gaming is advisable to counteract the negative effects on blood flow hemodynamics.NEW & NOTEWORTHY A 6-min light-intensity walking break during gaming can effectively combat the adverse effects of prolonged sitting, surpassing compression garments. Prolonged sitting reduces blood flow velocity, potentially leading to deep vein thrombosis (DVT). Compression sleeves help, with superior results after a 6-min walk at 60 min. Although compression stockings offer moderate improvements, a 6-min active break proves more effective. These findings offer promising interventions for gamers' health, initiating guidelines to mitigate DVT risk during gaming.

Comparisons of choroidal blood flow velocity between initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy.

Acute central serous chorioretinopathy (CSC) and Vogt-Koyanagi-Harada (VKH) disease in the acute uveitic phase are characterized by serous retinal detachment caused by dysfunction of the choroid. The aim of this study is to compare blood flow velocity and pulse waveform parameters in the choroid between these two diseases. In this study, 25 patients (50 eyes) with VKH disease, 21 patients (27 eyes) with CSC and 15 healthy controls (30 eyes) were studied. Laser speckle flowgraphy (LSFG) was performed at presentation. Choroidal mean blur rate (MBR), representing blood flow velocity in choroidal vessels, was significantly lower in the eyes affected by VKH disease compared with the healthy control and CSC eyes. CSC eyes had a significantly higher MBR compared with healthy controls. Among the analyzed pulse waveform parameters, blow-out time (BOT), falling rate (FR) and flow acceleration index (FAI) changed significantly. BOT value was significantly lower in CSC eyes than in healthy control and VKH eyes. FR and FAI values were significantly lower in VKH eyes than in healthy control and CSC eyes. There was a strong positive correlation between MBR and FAI. Our findings confirm different pathophysiology of these two diseases. Assessment of choroidal blood flow velocity and haemodynamics with LSFG provides useful information to differentiate acute CSC and initial-onset acute uveitis associated with VKH disease.

Noninvasive evaluation of pulmonary artery stiffness in heart failure patients via cardiovascular magnetic resonance

Heart failure (HF) presents manifestations in both cardiac and vascular abnormalities. Pulmonary hypertension (PH) is prevalent in up 50% of HF patients. While pulmonary arterial hypertension (PAH) is closely associated with pulmonary artery (PA) stiffness, the association of HF caused, post-capillary PH and PA stiffness is unknown. We aimed to assess and compare PA stiffness and blood flow hemodynamics noninvasively across HF entities and control subjects without HF using CMR. We analyzed data of a prospectively conducted study with 74 adults, including 55 patients with HF across the spectrum (20 HF with preserved ejection fraction [HFpEF], 18 HF with mildly-reduced ejection fraction [HFmrEF] and 17 HF with reduced ejection fraction [HFrEF]) as well as 19 control subjects without HF. PA stiffness was defined as reduced vascular compliance, indicated primarily by the relative area change (RAC), altered flow hemodynamics were detected by increased flow velocities, mainly by pulse wave velocity (PWV). Correlations between the variables were explored using correlation and linear regression analysis. PA stiffness was significantly increased in HF patients compared to controls (RAC 30.92 ± 8.47 vs. 50.08 ± 9.08%, p < 0.001). PA blood flow parameters were significantly altered in HF patients (PWV 3.03 ± 0.53 vs. 2.11 ± 0.48, p < 0.001). These results were consistent in all three HF groups (HFrEF, HFmrEF and HFpEF) compared to the control group. Furthermore, PA stiffness was associated with higher NT-proBNP levels and a reduced functional status. PA stiffness can be assessed non-invasively by CMR. PA stiffness is increased in HFrEF, HFmrEF and HFpEF patients when compared to control subjects.Trial registration The study was registered at the German Clinical Trials Register (DRKS, registration number: DRKS00015615).

Blood Flow Directs Yap/Taz-Mediated Transcriptional Regulation of Self-Renewal Programs to Control Developmental HSPC Expansion By Mechanical Stimulation of Piezo1

Hematopoietic stem and progenitor cells (HSPCs) emerge from artery-derived hemogenic endothelium (HE) in the vertebrate embryo during development. This process entails a cellular reprogramming from endothelial to hematopoietic gene signatures driven by the Runx1 transcription factor (TF), which is referred to as the endothelial-to-hematopoietic transition (EHT). A major goal of cellular therapeutics is to derive patient-specific HSPCs from iPSCs for clinical use, yet current differentiation protocols largely fail to recapitulate EHT to produce or expand long-lived multi-potent HSPCs in vitro suggesting an incomplete understanding of the in vivo regulatory cues. Physical forces of wall shear stress (WSS) and cyclic stretch (CS) produced by hemodynamic blood flow in embryos are one such cue required during EHT to generate HSPCs from HE, however the mechanisms by which these forces are sensed and converted into a “stemness” regulatory module remain undefined. Our previous work implicated the Hippo pathway TF YAP as essential for the maintenance, but not initiation, of the hematopoietic program in newly specified HE. Here, using scRNA-sequencing of sorted zebrafish trunk endothelial cells to capture all stages of EHT progression, we find that overexpression of YAP drives lipid metabolism, cell cycling, and propagation of a hematopoietic gene regulatory network (GRN) in the earliest specified HE cells. By employing a heat shock-inducible dominant negative YAP zebrafish line, we unmask a latent role for the YAP paralogue TAZ in hematopoiesis, which can promote CD41 + and Flk +/Myb + HSPC production upon reduced YAP function. YAP and TAZ initiate transcriptional responses downstream of mechanical stimuli and require DNA binding cofactors to regulate target genes. Surprisingly, luciferase assays in HEK293 cells demonstrated a potent synergistic effect of TAZ/RUNX1, but not YAP/RUNX1, in transcriptional regulation at RUNX enhancers. Finally, by pharmacologic and genetic manipulation, we identify the stretch-gated membrane ion channel Piezo1 as a potent regulator of CS-induced YAP/TAZ mechanotransduction in HE. Stimulation of zebrafish embryos with the Piezo1 small molecule agonist Yoda1 significantly increases HSPC number and YAP target gene expression in a YAP-dependent fashion. A similar modulation of blood and YAP target genes in human iPSC-derived CD34+ HE cells is seen with Yoda1, suggesting that this stretch-Piezo1-YAP axis can be chemically tuned in vitro to enhance HSPC differentiation. These results illuminate molecular details of how YAP/TAZ directs the production of HSPCs from HE in response to mechanical cues, and have broader implications for alternate regulatory effects of mechanically-stimulated Hippo TFs depending on the transcriptional milieu in cell-type specific contexts.

Reduced systolic flow efficacy in left ventricular dyssynchrony evident by blood speckle imaging

Abstract Introduction Intraventricular vortices facilitate efficient blood flow in a healthy heart. Changes in the blood flow pattern can cause energy loss and inefficient filling or ejection. Thus changes, or reduction in vorticity may therefore be of importance for cardiac function. Blood speckle imaging (BSI) is a novel blood flow visualization tool based on echocardiography, partially overcoming the angel dependency of conventional colour Doppler. BSI tracks speckles generated by the moving blood cells, similar to myocardial speckle tracking, but requires a very high frame rate limiting penetration. Dyssynchrony in left bundle branch block (LBBB) affects the systolic functions but there is limited insight into how LBBB alters the blood flow vorticity. Purpose We investigated the effect of dyssynchrony on blood flow hemodynamics using blood speckle imaging. Methods In eight anesthetized canine mongrels, left ventricular flow was visualized using BSI. A qualitative visual assessment of vortices during the cardiac cycle, together with a quantitative assessment based on kinetic energy loss and vorticity were made. Regional myocardial function parameters were measured by sonomicrometry. Peak septal flash strain in isovolumetric contraction (IVC) was measured by sonomicrometry (figure) as an indicator of dyssynchrony. Assessments were made at baseline, under right ventricular free wall pacing (RV pacing) mimicking LBBB, after induced LBBB by ablation and under cardiac resynchronization therapy (CRT). Results During IVC at baseline all animals had a central ventricular vortex. However during RV pacing and LBBB it was distorted in various patterns. RV pacing significantly reduced the number of vortices in systole and disrupted the central vortex in IVC (1.0±0.0 vs 0.4±0.5, p=0.01). Energy loss (EL) in systole increased (40.2±12.5 vs 55.3±23.3 mW/m, p&amp;lt;.05). Septal end systolic strain was significantly reduced (-8.8±5.1 vs -1.9±7.3 %, p&amp;lt;0.01) and septal flash strain was significantly increased (1.0±1.4 vs 7.7±3.6 and 6.6±3.8 [ER1] [ER2] %, p&amp;lt;0.01) in RV pacing and LBBB. CRT caused a realignment of the central vortex (0.8±0.5 vs0.3±0.5, p=0.03). The change in energy loss was not significant, but numerically reduced (55.4±38.8 vs 76.4±48.9 mW/m, p=0.06). See table and figure 1. Conclusions The main systolic vortex in IVC was disrupted during septal flash by RV pacing and LBBB, altering the flow pattern compared to baseline. The resultant unstructured flow pattern had increased energy loss in systole, indicating a less efficient flow pattern and less preservation of energy. It should be further explored if this is of importance to understand the reduced LV function and LV remodelling during dyssynchrony.Figure 1Table 1

Non-Newtonian pulsatile blood flow through the stenosed arteries: comparison between the viscoelastic and elastic arterial wall in response to the alterations

:In this study, we investigate the impact of aortic stenosis on the hemodynamics of pulsatile blood flow within a 3D aortic model. Employing a non-Newtonian Casson model with a hematocrit of 45%, our study introduces a preliminary hypothesis to simulate blood flow dynamics, incorporating both linear elastic and viscoelastic models to define the mechanical characteristics of the artery. Through simulations conducted with Ansys-Cfx (version 15), we utilize a 2-way fluid-structure interaction (FSI) approach, employing a Lagrangian-Eulerian formulation with second-order accuracy. We explore the influence of stenosis severity on variables including velocity profiles, pressure distribution, shear stress, wall displacement, and changes in the OSI parameter. Our investigation encompasses arteries with both elastic and viscoelastic walls. The key findings that arise from our results highlight the viscoelastic model’s demonstration of reduced radial wall displacement when compared to the linear elastic model. Additionally, we observe that elevated arterial stenosis percentages lead to the elongation of vortex length, heightened wall shear stress, and increased slope of velocity profiles downstream of the stenosed region. Furthermore, bulky obstruction of viscoelastic arteries as opposed to elastic, resulted in a maximum 5 percent increase in velocity profile and a 29.6% decrease in radial displacement. The zenith of shear stress occurs concomitantly with the velocity’s peak within the stenosed area. Viscoelastic arterial wall shear stress at the stenosis site escalates due to the rapid expansion of the stenosis. The viscoelastic wall, responding with a blend of viscous and elastic characteristics to applied stress, undergoes slight deformation in shape. Following stress reduction, the wall gradually reverts to its original form, thus alleviating some of the applied stress. In contrast, the elastic wall retains its altered shape due to stress preservation within the material. Additionally, we ascertain an augmentation in radial displacement corresponding with increased artery stenosis.

Computational modeling of blood clot lysis considering the effect of vessel wall and pulsatile blood flow.

Stroke is one of the major causes of global death, which can occur due to blockage in a blood vessel by a clot. The immediate dissolving of the clot is essential to restore the blood flow and prevent tissue necrosis. Clot dissolution can be achieved via thrombolytic therapy using plasminogen activators. In this study, a clot dissolution model is developed for a three-dimensional patient-specific carotid artery that investigates the effect of different vessel wall models on clot dissolution. The lysis pattern of the clot and hemodynamics of blood flow are evaluated using three different models of the vessel wall, namely, rigid, linear elastic, and Mooney-Rivlin hyperelastic. The effect of flow condition is considered by solving the Navier-Stokes equationsfor the free flow domain and the Brinkman equationfor the clot domain with the same pressure and velocity fields. This will result in continuous pressure and velocity over the interfaces of the free flow and clot domains. The blood inflow is assumed to be pulsatile. In addition, the species transport driven by diffusion and convection is considered to be different in the porous medium and plasma. The obtained results show that in all models, the starting time of clot volume decrease is almost the same and the clot starts dissolving from the inner curvature of the artery. However, in the hyperelastic model, dissolving the clot takes longer compared to the other two models. By monitoring the vessel wall deformation, the exact time of vessel recanalization is determined.