Physiological Flow Research Articles

Vortex dynamics and transport phenomena in stenotic aortic models using Echo-PIV

Atherosclerosis is the most fatal cardiovascular disease. As disease progresses, stenoses grow inside the arteries blocking their lumen and altering blood flow. Analysing flow dynamics can provide a deeper insight on the stenosis evolution. In this work we combined Eulerian and Lagrangian descriptors to analyze blood flow dynamics and fluid transport in stenotic aortic models with morphology, mechanical and optical properties close to those of real arteries. To this end, vorticity, particle residence time (PRT), particle's final position (FP) and finite time Lyapunov's exponents (FTLE) were computed from the experimental fluid velocity fields acquired using ultrasonic particle imaging velocimetry (Echo-PIV). For the experiments, CT-images were used to create morphological realistic models of the descending aorta with 0%, 35% and 50% occlusion degree with same mechanical properties as real arteries. Each model was connected to a circuit with a pulsatile programmable pump which mimics physiological flow and pressure conditions. The pulsatile frequency was set to ≈0.9 Hz (55 bpm) and the upstream peak Reynolds number (Re) was changed from 1100 to 2000. Flow in the post-stenotic region was composed of two main structures: a high velocity jet over the stenosis throat and a recirculation region behind the stenosis where vortex form and shed. We characterized vortex kinematics showing that vortex propagation velocity increases with Re. Moreover, from the FTLE field we identified Lagrangian coherent structures (i.e. material barriers) that dictate transport behind the stenosis. The size and strength of those barriers increased with Re and the occlusion degree. Finally, from the PRT and FP maps, we showed that independently of Re, the same amount of fluid remains on the stenosis over more than a pulsatile period.

Histone deacetylase 1 controls CD4+ T cell trafficking in autoinflammatory diseases.

CD4+ T cell trafficking is a fundamental property of adaptive immunity. In this study, we uncover a novel role for histone deacetylase 1 (HDAC1) in controlling effector CD4+ T cell migration, thereby providing mechanistic insight into why a T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis (EAE). HDAC1-deficient CD4+ T cells downregulated genes associated with leukocyte extravasation. In vitro, HDAC1-deficient CD4+ T cells displayed aberrant morphology and migration on surfaces coated with integrin LFA-1 ligand ICAM-1 and showed an impaired ability to arrest on and to migrate across a monolayer of primary mouse brain microvascular endothelial cells under physiological flow. Moreover, HDAC1 deficiency reduced homing of CD4+ T cells into the intestinal epithelium and lamina propria preventing weight-loss, crypt damage and intestinal inflammation in adoptive CD4+ T cell transfer colitis. This correlated with reduced expression levels of LFA-1 integrin chains CD11a and CD18 as well as of selectin ligands CD43, CD44 and CD162 on transferred circulating HDAC1-deficient CD4+ T cells. Our data reveal that HDAC1 controls T cell-mediated autoimmunity via the regulation of CD4+ T cell trafficking into the CNS and intestinal tissues.

Microheart: A microfluidic pump for functional vascular culture in microphysiological systems

Advances in microphysiological systems have prompted the need for long-term cell culture under physiological flow conditions. Conventional laboratory pumps typically lack the ability to deliver cell culture media at the low flow rates required to meet the physiological ranges of fluid flow, and are often pulsatile or require flow reversal. Here, a microfluidic-based pump is presented, which allows for the controlled delivery of media for vascular microphysiological applications. The performance of the pump was characterized in a range of microfluidic systems, including straight channels of varying dimensions and self-assembled microvascular networks. A theoretical framework was developed based on lumped element analysis to predict the performance of the pump for different fluidic configurations and a finite element model of the included check-valves. The use of the pump for microvascular physiological studies demonstrated the utility of this system to recapitulate vascular fluid transport phenomena in microphysiological systems, which may find applications in disease models and drug screening.

RAMP2-AS1 Regulates Endothelial Homeostasis and Aging.

The homeostasis of vascular endothelium is crucial for cardiovascular health and endothelial cell (EC) aging and dysfunction could negatively impact vascular function. Leveraging transcriptome profiles from ECs subjected to various stimuli, including time-series data obtained from ECs under physiological pulsatile flow vs. pathophysiological oscillatory flow, we performed principal component analysis (PCA) to identify key genes contributing to divergent transcriptional states of ECs. Through bioinformatics analysis, we identified that a long non-coding RNA (lncRNA) RAMP2-AS1 encoded on the antisense of RAMP2, a determinant of endothelial homeostasis and vascular integrity, is a novel regulator essential for EC homeostasis and function. Knockdown of RAMP2-AS1 suppressed RAMP2 expression and caused EC functional changes promoting aging, including impaired angiogenesis and increased senescence. Our study demonstrates an integrative approach to quantifying EC aging based on transcriptome changes, which also identified a number of novel regulators, including protein-coding genes and many lncRNAs involved EC functional modulation, exemplified by RAMP2-AS1.

Blood flow characteristics after aortic valve neocuspidization in paediatric patients: a comparison with the Ross procedure.

AimsThe aortic valve (AV) neocuspidization (Ozaki procedure) is a novel surgical technique for AV disease that preserves the natural motion and cardiodynamics of the aortic root. In this study, we sought to evaluate, by 4D-flow magnetic resonance imaging, the aortic blood flow characteristics after AV neocuspidization in paediatric patients.Methods and resultsAortic root and ascending aorta haemodynamics were evaluated in a population of patients treated with the Ozaki procedure; results were compared with those of a group of patients operated with the Ross technique. Cardiovascular magnetic resonance studies were performed at 1.5 T using a 4D flow-sensitive sequence acquired with retrospective electrocardiogram-gating and respiratory navigator. Post-processing of 4D-flow analysis was performed to calculate flow eccentricity and wall shear stress. Twenty children were included in this study, 10 after Ozaki and 10 after Ross procedure. Median age at surgery was 10.7 years (range 3.9–16.5 years). No significant differences were observed in wall shear stress values measured at the level of the proximal ascending aorta between the two groups. The analysis of flow patterns showed no clear association between eccentric flow and the procedure performed. The Ozaki group showed just a slightly increased transvalvular maximum velocity.ConclusionProximal aorta flow dynamics of children treated with the Ozaki and the Ross procedure are comparable. Similarly to the Ross, Ozaki technique restores a physiological laminar flow pattern in the short-term follow-up, with the advantage of not inducing a bivalvular disease, although further studies are warranted to evaluate its long-term results.

Music for pain in healthy neonates

Background The neonatal pain threshold is 30-50% lower than in adults and older children because of immature pain inhibition function in nervous centers. Acute pain in neonates results in behavioral, physiological, and cerebral blood flow changes that may lead to intraventricular bleeding and periventricular leukomalacia. Music is believed to reduce pain perception as it distracts, influencing the parasympathetic and sympathetic nervous system by decreasing pulse rate, blood pressure, and breathing, hence, promoting a relaxed state.
 Objective To evaluate effects of music intervention on physiological parameters and pain perception in healthy newborns undergoing a painful medical procedure (immunization injection).
 Methods This was a double-blind, randomized control trial study. A recorded instrumental lullaby “Nina Bobo” was given for 5 minutes to the music group and no music for control, prior injection of Hepatitis B 0. The evaluation of heart rate and SpO2 were performed at baseline, 30 seconds, and 5 minutes after injection. Pain perception were measured by Neonatal Infant Pain Scale (NIPS) at 30 seconds and 5 minutes after injection.
 Results Total of 51 subjects were enrolled. There were no difference of SpO2 and NIPS between both music and control groups. Music improved heart rate after 30 seconds and 5 minutes after injection, median 126 (range 55-149) bpm from median 136 (range 78-154) bpm, and even lower than baseline [mean 128.9 (SD 12.5) bpm; P=0.019]. The control showed no improvement of heart rate mean 124,34 (SD 18,45) from 124,73 (SD 18,39); P=0.875There were no significant differences between the 2 groups.
 Conclusion Music is not effective in improving oxygen saturation, heart rate, and is not effective in reducing the degree of pain.

Implementation of a Human Renal Proximal Tubule on a Chip for Nephrotoxicity and Drug Interaction Studies.

Proximal tubule epithelial cells (PTEC) are susceptible to drug-induced kidney injury (DIKI). Cell-based, two-dimensional (2D) invitro PTEC models are often poor predictors of DIKI, probably due to the lack of physiological architecture and flow. Here, we assessed a high throughput, 3D microfluidic platform (Nephroscreen) for the detection of DIKI in pharmaceutical development. This system was established with four model nephrotoxic drugs (cisplatin, tenofovir, tobramycin and cyclosporin A) and tested with eight pharmaceutical compounds. Measured parameters included cell viability, release of lactate dehydrogenase (LDH) and N-acetyl-β-d-glucosaminidase (NAG), barrier integrity, release of specific miRNAs, and gene expression of toxicity markers. Drug-transporter interactions for P-gp and MRP2/4 were also determined. The most predictive read outs for DIKI were a combination of cell viability, LDH and miRNA release. In conclusion, Nephroscreen detected DIKI in a robust manner, is compatible with automated pipetting, proved to be amenable to long-term experiments, and was easily transferred between laboratories. This proof-of-concept-study demonstrated the usability and reproducibility of Nephroscreen for the detection of DIKI and drug-transporter interactions. Nephroscreen it represents a valuable tool towards replacing animal testing and supporting the 3Rs (Reduce, Refine and Replace animal experimentation).

Estimating blood flow velocity using time-resolved 3D angiography and a derived physical law of contrast media

Objective. Four-dimensional (4D) digital subtraction angiography (DSA) offers a method for evaluating hemodynamics. It is, however, unclear how the delivered contrast medium interacts with the physiological blood flow, and how hemodynamic information may be inferred from the mixture of the contrast medium and blood. In this study, we present a theoretical explanation of contrast dynamics, and an accompanying algorithm for estimating blood flow velocity. Approach. We retrospectively recruited 23 patients who underwent both 4D DSA and magnetic resonance (MR) phase-contrast imaging. The 4D DSA-reconstructed contrast dynamics were first studied for the internal carotid arteries. Using physical laws governing fluid motion within a curved tube, we showed that the reconstructed contrast dynamics obeyed a simple advection equation. We then proposed an algorithm for estimating the contrast dynamics using angiographic data, and subsequently estimated the axial blood flow velocity using an advection equation. Main results. The estimated velocities were compared using three techniques: the Fourier technique, Lin’s method, and MR phase contrast. Testing with noise-corrupted artificial data showed that the proposed algorithm was noise resistant. The velocities of 23 patients computed by 4D DSA using the proposed algorithm showed a moderate correlation with the MR phase contrast (r = 0.61), and good correlations with the other two techniques (r = 0.75 and r = 0.72). Significance. The proposed algorithm and has been applied to blood vessel segments with poor signal-to-noise ratios and axial lengths of less than 3 cm, and has a physical basis for computing axial flow velocities using an advection equation. The results of the proposed algorithm are consistent with existing methods.

Limb Volume Reduction and Infection Outcomes Following Vascularized Lymph Node Transfer for Cancer Treatment-Related Lymphoedema: A Systematic Review and Meta-Analysis

Background: Cancer treatment-related lymphoedema (CTRL) is a chronic and disabling complication that carries a significant health burden during cancer survivorship. Vascularized lymph node transfer (VLNT) is a novel surgical technique utilised to reconstruct physiological lymphatic flow in lymphoedematous limbs. In this study, we set out to synthesise and assess the efficacy of VLNT for reducing limb volume and infection outcomes in CTRL Methods :In this systematic review and meta-analysis, we searched PubMed, Medline and EMBASE databases until 2019 for English-language full-text articles. Studies that reported VLNT as the sole therapeutic intervention for the management of cancer treatment-related lymphoedema and provided volumetric limb and/or patient-reported lymphatic quality of life and/or cellulitis-related outcomes were included. All studies were scored for methodological quality (STROBE and CONSORT checklists) and lymphoedema-specific data reporting quality. Using a random-effects model, we estimated the pooled limb volume reduction and 95% CI for upper and lower limbs stratifying according to site of measurement and VLNT donor. We also estimated the pooled reduction in cellulitis episodes and mean improvement in lymphoedema-related quality of life. PROSPERO registration number: CRD42020204080. Findings: Our search strategy identified 277 articles, of which thirty-one studies (25 cohort studies, 1 randomised controlled study, 2 case reports, 2 case-series and 1 cross-sectional patient survey) encompassing 581 patients satisfied the inclusion criteria. The overall methodological quality of studies was assessed to be low. Meta-analysis demonstrated that performing VLNT for CTRL led to limb volume reductions in both upper limb (above elbow circumferential reduction rates (CRR AE ) = 42.7 % (95% CI: 36.5-48.8, I 2 : 94.3 %, p = 0.000, 153 patients, 10 studies); below elbow CRR (CRR BE ) = 34.1 % (95% CI: 33.0-35.1, I 2 : 0.0 %, p = 0.919, 144 patients, 9 studies)) and lower limb (above knee CRR (CRR AK ) = 46.8 % (95% CI: 43.2-50.4, I 2 : 92.4 %, p = 0.000 26 patients, 3 studies); below knee (CRR BK ) = 54.6 % (95% CI: 39.0-70.2, I 2 : 97.6%, p = 0.000, 26 patients, 3 studies)), respectively. Extra-abdominal VLNT, abdominal VLNT and autologous breast reconstruction with VLNT led to CRRs of 49.5 % (95% CI: 46.5-52.5, I 2 : 8.3 %, p = 0.365, 7 studies, 108 patients), 39.6 % (95% CI: 37.2-42.0, I 2 : 89.5 %, p = 0.000, 3 studies, 15 patients) and 32.7 % (95% CI: 11.1-54.4, I 2 : 96.9 %, p = 0.000 3 studies, 29 patients). Performing VLNT resulted in a mean reduction in cellulitis episodes of 2.1 episodes (95% CI: -2.7- -1.4) per annum. The mean improvement in lymphoedema-related quality of life was found to be 4.26 (LYMQOL “overall domain”). Interpretation: VLNT for CTRL can achieve reductions in limb volume and episodes of cellulitis in both upper and lower limbs suggesting it is an effective therapy. However, published studies were methodologically heterogeneous and of low quality highlighting the need for standardised outcome reporting and further well-designed randomised controlled trials comparing VLNT against existing therapies. Funding Statement: There was no funding source for this study. Declaration of Interests: We declare no competing interests.

Label-free multimodal quantitative imaging flow assay for intrathrombus formation in vitro

Microfluidics in vitro assays recapitulate a blood vessel microenvironment using surface-immobilized agonists under biofluidic flows. However, these assays do not quantify intrathrombus mass and activities of adhesive platelets at the agonist margin and use fluorescence labeling, therefore limiting clinical translation potential. Here, we describe a label-free multimodal quantitative imaging flow assay that combines rotating optical coherent scattering microscopy and quantitative phase microscopy. The combined imaging platform enables real-time evaluation of membrane fluctuations of adhesive-only platelets and total intrathrombus mass under physiological flow rates in vitro. We call this multimodal quantitative imaging flow assay coherent optical scattering and phase interferometry (COSI). COSI records intrathrombus mass to picogram accuracy and shape changes to a platelet membrane with high spatial-temporal resolution (0.4 μm/s) under physiological and pathophysiological fluid shear stress (1800 and 7500 s−1). With COSI, we generate an axial slice of 4 μm from the coverslip surface, approximately equivalent to the thickness of a single platelet, which permits nanoscale quantification of membrane fluctuation (activity) of adhesive platelets during initial adhesion, spreading, and recruitment into a developing thrombus (mass). Under fluid shear, pretreatment with a broad range metalloproteinase inhibitor (250 μM GM6001) blocked shedding of platelet adhesion receptors that shown elevated adhesive platelet activity at average of 42.1 μm/s and minimal change in intrathrombus mass.

Feasibility of a Dielectric Elastomer Augmented Aorta.

Although heart transplantation is a gold standard for severe heart failure, there is a need for alternative effective therapies. A dielectric‐elastomer aorta is used to augment the physiological role of the aorta in the human circulatory system. To this end, the authors developed a tubular dielectric elastomer actuator (DEA) able to assist the heart by easing the deformation of the aorta in the systole and by increasing its recoil force in the diastole. In vitro experiments using a pulsatile flow‐loop, replicating human physiological flow and pressure conditions, show a reduction of 5.5% (47 mJ per cycle) of the heart energy with this device. Here, the controlled stiffness of the DEA graft, which is usually difficult to exploit for actuators, is perfectly matching the assistance principle. At the same time, the physiological aortic pressure is exploited to offer a prestretch to the DEA which otherwise would require an additional bulky pre‐stretching system to reach high performances.

Blood Flow Modeling in Coronary Arteries: A Review

Atherosclerosis is one of the main causes of cardiovascular events, namely, myocardium infarction and cerebral stroke, responsible for a great number of deaths every year worldwide. This pathology is caused by the progressive accumulation of low-density lipoproteins, cholesterol, and other substances on the arterial wall, narrowing its lumen. To date, many hemodynamic studies have been conducted experimentally and/or numerically; however, this disease is not yet fully understood. For this reason, the research of this pathology is still ongoing, mainly, resorting to computational methods. These have been increasingly used in biomedical research of atherosclerosis because of their high-performance hardware and software. Taking into account the attempts that have been made in computational techniques to simulate realistic conditions of blood flow in both diseased and healthy arteries, the present review aims to give an overview of the most recent numerical studies focused on coronary arteries, by addressing the blood viscosity models, and applied physiological flow conditions. In general, regardless of the boundary conditions, numerical studies have been contributed to a better understanding of the development of this disease, its diagnosis, and its treatment.

Channel flow of MHD bingham fluid due to peristalsis with multiple chemical reactions: an application to blood flow through narrow arteries

The present analysis emphasizes the effects of variable properties on Bingham fluid under MHD peristaltic transport. Due to the impact of mechanical forces on the applied magnetic field on the conducting fluid, the fluid stream gets altered. These principle targets drug transport and control of blood flow during surgeries; hence the impact of MHD flow with convective and porous boundary conditions is considered. Further, the implications of homogeneous and heterogeneous reactions are analyzed by considering wall properties. The governing equations are turned dimensionless by appropriate similarity transformations. The series solution is obtained for temperature, velocity, and concentration by perturbation method with lubrication approach. The graphical representation of the pertinent parameters on the physiological flow quantities is depicted by applying for MATLAB 2019b program. The obtained results reveal that the rise in the magnetic parameter diminishes the velocity and temperature profiles. Further, the impact of variable viscosity slightly improves the magnitude of the trapped bolus. The homogenous and heterogeneous reaction parameters have a converse effect on the concentration distribution. Moreover, the present investigation finds its applications to perceive the complex rheological functioning of blood flow through narrow arteries.

Pulsatile Flow-Induced Fatigue-Resistant Photopolymerizable Hydrogels for the Treatment of Intracranial Aneurysms.

An alternative intracranial aneurysm embolic agent is emerging in the form of hydrogels due to their ability to be injected in liquid phase and solidify in situ. Hydrogels have the ability to fill an aneurysm sac more completely compared to solid implants such as those used in coil embolization. Recently, the feasibility to implement photopolymerizable poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogels in vitro has been demonstrated for aneurysm application. Nonetheless, the physical and mechanical properties of such hydrogels require further characterization to evaluate their long-term integrity and stability to avoid implant compaction and aneurysm recurrence over time. To that end, molecular weight and polymer content of the hydrogels were tuned to match the elastic modulus and compliance of aneurysmal tissue while minimizing the swelling volume and pressure. The hydrogel precursor was injected and photopolymerized in an in vitro aneurysm model, designed by casting polydimethylsiloxane (PDMS) around 3D printed water-soluble sacrificial molds. The hydrogels were then exposed to a fatigue test under physiological pulsatile flow, inducing a combination of circumferential and shear stresses. The hydrogels withstood 5.5 million cycles and no significant weight loss of the implant was observed nor did the polymerized hydrogel protrude or migrate into the parent artery. Slight surface erosion defects of 2–10 μm in depth were observed after loading compared to 2 μm maximum for non-loaded hydrogels. These results show that our fine-tuned photopolymerized hydrogel is expected to withstand the physiological conditions of an in vivo implant study.

ROLE OF HYPERBILIRUBINEMIA, ELEVATED CREACTIVE PROTEIN AND LEUCOCYTE COUNT AS A PREDICTIVE FACTOR FOR APPENDICEAL PERFORATION IN ACUTE APPENDICITIS

Background: Appendiceal perforation in patients with acute appendicitis may cause a variety of potentially life-threatening complications. Escherichia coli endotoxin has been shown to impact physiological bile flow in vivo. This had led to the theory that hyperbilirubinemia and elevated CRP in patients with appendicitis may have a predictive potential for the preoperative diagnosis of appendiceal perforation. Objectives: The aim of this retrospective study was to investigate the diagnostic value of hyperbilirubinemia and elevated CRP as a preoperative laboratory marker for appendiceal perforation in patients with acute appendicitis. Thus a new marker for appendiceal perforation would be welcomed. Thus, the need for the study is to conclude whether the Serum Bilirubin or CRP can be considered as a new laboratory marker to aid in the diagnosis of Appendicular Perforation. Materials and methods: All patients admitted with clinical diagnosis of "Acute Appendicitis" or "Appendicular Perforation" and undergoing surgery in General Surgery Dept in Tertiary Care Teaching Hospital were taken as Subjects for this study. The primary data for this study were the blood investigations of the patients. 200 patients with concerned consent and meeting the inclusion criteria were included in the study. The necessary clinical and lab details were obtained in a prewritten format. The intraoperative findings were noted and documented precisely. Upon completion of data collection the preoperative bilirubin levels of the perforated and uncomplicated groups wereOther clinical and lab parameters obtained during the study were compared between the two groups. All parameters were subjected to statistical analysis and evaluated critically. Results: A total of 200 patients participated in the study. Of the 200 patients studied 132 patients were males and 68 patients were females. The youngest patient was 13 years old and the oldest 64 years. Among all the patients operated with a diagnosis of Acute Appendicitis 92 were found to have a perforated appendix, and 108 were found to have a non-perforated appendix. It was observed that among 92 patients with perforated appendix 86 patients showed a raised CRP levels and 58 patients had a raised Bilirubin levels. However in case of non-perforated cases it was found that among the 108 cases 82 patients had a raised CRP levels and 36 patients showed raised bilirubin levels. Conclusion: Hence Logistic Regression technique revealed that the C- reactive protein and Hyperbilirubinemia can be used to predict the appendicular perforation preoperatively and that their roles are comparable and that there is no definitive advantage of one over the other for the same.

Development, calibration, and testing of 3D amplified MRI (aMRI) for the quantification of intrinsic brain motion

Microvascular blood volume pulsations, combined with CSF circulation result in subtle deformation of the brain during each heartbeat. To visualize and quantify these small deformations, an image processing technique called amplified MRI (aMRI) was recently introduced. aMRI, however, is unable to visualize the 3-directional deformation of the human brain, which is caused by the physiological flow and its biomechanical coupling with the brain. Addressing this issue, we extended 2D aMRI to 3D, which allows visualization of the subtle motion in 3-directions. First, we validated 3D aMRI’s ability to measure out-of-plane motion while simultaneously increasing SNR in digital phantoms mimicking the brain’s deformation. We then applied 2D and 3D aMRI to 3D cine MRI of 6 healthy subjects and found approximately 80% higher temporal SNR in the 3D aMRI outputs with SNR =26.8±8.3 compared to the 2D aMRI with SNR =15.1±2.6 (p<0.01). 3D displacement maps and their dominant modeshapes were extracted, which demonstrated physiologically meaningful patterns of motion in response to heart pulsatility and CSF circulation. We observed the peak superior-inferior displacement near the pons and midbrain. Peak medial-lateral and anterior-posterior displacement were observed close to the 3rd and lateral ventricles. Interestingly, the modeshapes showed an almost symmetrical expansion of the brain with 33%±4%,38%±4%, and 29%±7% of the deformation being predominantly towards superior-inferior, anterior-posterior, and medial-lateral, respectively (p<0.01). These preliminary results hint at 3D aMRI’s versatility and translatability for providing novel biomechanical imaging markers, which could simplify diagnostics and enable a deeper understanding of the biomechanics of a wide-range of pathophysiological conditions. Statement of significanceThe brain has very soft material properties and is under constant deformation as a result of physiological flow and its biomechanical coupling with the tissue. In this work, a novel image processing algorithm called 3D aMRI is introduced which allows visualization and quantification of this very subtle motion. After validation of the algorithm using digital phantom models, 3D aMRI was applied to in vivo 3D cine MRI data. This allowed measurement of the brain’s subtle deformation as a response of heart pulsatility and CSF circulation, which might hold essential information regarding the physiological state of the brain tissue. 3D aMRI is a post-processing algorithm carried out on standard imaging data. We believe that due to its versatility and translatability, it could simplify diagnostics and enable a deeper understanding of the biomechanics of a wide range of pathophysiological conditions.

Preliminary study of the effect of hemolysis on platelet aggregation through microscopic observation under physiological shear flow

Preliminary study of the effect of hemolysis on platelet aggregation through microscopic observation under physiological shear flow

Aging-Related Structural and Functional Changes in Cerebral Arteries: Caloric Restriction (CR) Intervention

Cerebral arteries play a crucial role in the regulation of blood flow to the brain to satisfy the demand of oxygen and glucose for proper function of the organ. Physiological cerebral blood flow (CBF) is maintained within a normal range in response to changes in blood pressure a mechanism named Cerebral Blood Flow Auto Regulation (CBFAR). Structure and function of cerebral arteries have an important impact on CBFAR. Several studies in human and animals have showed significant morphological and functional changes in cerebral vessels of aged brain associated with a reduced CBF which is also impaired in cerebrovascular pathology linked to brain diseases. Interestingly, one new emergent aspect is the lifelong Calorie Restriction (CR) as a potential intervention to prevent age-related cerebral artery changes and preserve the health of aging brain. This review summarizes the recent literature on the effects of aging on cerebral artery structure and function and the potential of CR as opportunities for prevention and treatment

Krónikus teljes koronáriaokklúzió transthoracalis echokardiográfiás diagnózisa

We report a case of a 59 years old male patient who reported chronic effort chest pain. Transthoracic Doppler echocardiography (TTDE) presented normal left ventricular systolic function with retrograde coronary artery blood flow in the distal and middle part of the left anterior descending artery (LAD). On the basis of findings of TTDE, we suspected chronic total occlusion (CTO) of the LAD, which was confirmed by invasive coronary angiography. The LAD CTO was successfully opened by a catheter-based intervention. After the percutaneous coronary intervention, the patient became completely free of symptoms. The repeated TTDE study showed the cessation of reverse coronary blood flow and the return of the physiological antegrade flow in the LAD.

Computational Fluid Dynamics Simulations at Micro-Scale Stenosis for Microfluidic Thrombosis Model Characterization

Platelet aggregation plays a central role in pathological thrombosis, preventing healthy physiological blood flow within the circulatory system. For decades, it was believed that platelet aggregation was primarily driven by soluble agonists such as thrombin, adenosine diphosphate and thromboxane A2. However, recent experimental findings have unveiled an intriguing but complementary biomechanical mechanism—the shear rate gradients generated from flow disturbance occurring at sites of blood vessel narrowing, otherwise known as stenosis, may rapidly trigger platelet recruitment and subsequent aggregation. In our Nature Materials 2019 paper [1], we employed microfluidic devices which incorporated micro-scale stenoses to elucidate the molecular insights underlying the prothrombotic effect of blood flow disturbance. Nevertheless, the rheological mechanisms associated with this stenotic microfluidic device are poorly characterized. To this end, we developed a computational fluid dynamics (CFD) simulation approach to systematically analyze the hemodynamic influence of bulk flow mechanics and flow medium. Grid sensitivity studies were performed to ensure accurate and reliable results. Interestingly, the peak shear rate was significantly reduced with the device thickness, suggesting that fabrication of microfluidic devices should retain thicknesses greater than 50 µm to avoid unexpected hemodynamic aberration, despite thicker devices raising the cost of materials and processing time of photolithography. Overall, as many groups in the field have designed microfluidic devices to recapitulate the effect of shear rate gradients and investigate platelet aggregation, our numerical simulation study serves as a guideline for rigorous design and fabrication of microfluidic thrombosis models.