Human Vascular System Research Articles

Transient CFD Modeling of Blood Flow Simulation through Left Coronary Artery

From the past twenty years, cardiac strokes have become one of the most common causes of death. Coronary artery disease means blockage of at least one course that supplies blood to the heart. These blockages are caused by the accumulation of plaque in the artery walls. That LDL cholesterol can restrict blood flow in the arteries and it directs to myocardial infarction; The CFD simulation is increasingly performed to study fluid phenomena inside the human vascular system. This simulation aims to develop a CFD model of coronary arteries and observe blood through the arteries, Estimate some of the hemodynamic parameters of the blood during the systolic and diastolic phase hemodynamic parameters were quantified and flow patterns are visualized visualized using CFD in the presence of plaques and forecast pressure rate, velocity in the arteries.

3D Transient CFD Modelling of Blood Flow through Coronary Artery

Over the past few decades, stroke has become one of the most common cause deaths. The heart muscle, like every other organ or tissue in our body, needs oxygen-rich blood to survive. Coronary artery disease means narrowing of the coronary arteries. This narrowing is due to a buildup of plaque in the walls of the arteries. Computational simulations provide invaluable information that is extremely difficult to obtain experimentally and is one of the many CFD sample applications in the biomedical area in which blood flow through an abnormal artery can be predicted. CFD analysis is increasingly performed to study fluid phenomena inside the human vascular system. In this paper, the study is to develop 3D CFD model of the Coronary artery to observe the blood flow through artery and estimate some of the hemodynamic parameters of blood during systolic and diastolic phase with plaque formation in artery. Hemodynamic parameters were quantified and flow patterns are visualized in the presence of plaques by using CFD.

Radio-Frequency ‘Magnetic-Field’ Probes Based on the Single Layer Flat Coil Oscillators - New Type of SFCO-Sensors for Bio-Medical Investigations

The physical principles and advantages of the use of a new class of the SFCO sensors (radio-frequency ‘magnetic-field’ probes) for the investigation of biomedical signals are discussed. The perspectivity of their application for the investigation of dynamic changes of dielectric characteristics of tissues and the medium of the organism is demonstrated. Data related to the registration of the state of the human vascular system by the use of such sensors are presented.

Integrating Flexible Electrochemical Sensor into Microfluidic Chip for Simulating and Monitoring Vascular Mechanotransduction.

As an interface between the blood flow and vessel wall, endothelial cells (ECs) are exposed to hemodynamic forces, and the biochemical molecules released from ECs-blood flow interaction are important determinants of vascular homeostasis. Versatile microfluidic chips have been designed to simulate the biological and physiological parameters of the human vascular system, but in situ and real-time monitoring of the mechanical force-triggered signals during vascular mechanotransduction still remains a significant challenge. Here, such challenge is fulfilled for the first time, by preparation of a flexible and stretchable electrochemical sensor and its incorporation into a microfluidic vascular chip. This allows simulating of in vivo physiological and biomechanical parameters of blood vessels, and simultaneously monitoring the mechanically induced biochemical signals in real time. Specifically, the cyclic circumferential stretch that is actually exerted on endothelium but is hard to reproduce in vitro is successfully recapitulated, and nitric oxide signals under normal blood pressure, as well as reactive oxygen species signals under hypertensive states, are well documented. Here, the first integration of a flexible electrochemical sensor into a microfluidic chip is reported, therefore paving a way to evaluate in vitro organs by built-in flexible sensors.

Vitamin D and cardiovascular disorders.

Vitamin D is necessary for bone health but may also have many extra-skeletal effects. The vitamin D endocrine system has major effects on gene and protein expression in many cells and tissues related to the cardiovascular system. In addition, many preclinical studies in animals with vitamin D deficiency or genetically silenced expression of the vitamin D receptor or vitamin D metabolizing enzymes suggest that the absence of vitamin D action may result in cardiovascular events. This includes dysfunctions of endothelial cells, thereby accelerating the process of atherosclerosis, hypertension or abnormal coagulation, ultimately resulting in higher risks for all major cardiovascular or cerebrovascular events. A wealth of observational studies in different parts of the world have fairly consistently found a strong association between a poor vitamin D status and surrogate markers or hard cardiovascular events. A few Mendelian randomization studies did, however, not find a link between genetically lower serum 25OHD concentrations and cardiovascular events. Finally, many RCTs could not demonstrate a consistent effect on surrogate markers, and a limited number of RCTs did so far not find whatever effect on hard cardiovascular endpoints such as myocardial ischemia or infarction, stroke, or cardiovascular death. In conclusion, preclinical data generated a plausible hypothesis of a link between vitamin D status and extra-skeletal events, including cardiovascular endpoints. Whether the vitamin D endocrine system is redundant for the human vascular system or whether the RCTs have not been optimally designed to answer the research question is thus not yet settled.

Driving complex flow waveforms with a linear voice coil actuator.

Oscillatory and pulsatile fluid flows for use in microfluidic applications were generated using a deformable chamber driven by a low cost linear voice coil actuator. Compliance in the fluidic system originating in the deformable chamber and the fluidic tubing produced a strong frequency dependence in the relationship between the system's input and the output flow rate. The effects of this frequency dependence were overcome by precise system calibration, enabling on-demand generation of sinusoidal oscillations in the fluid flow rate with a controlled amplitude in the range from 0.1 to over 1 ml/min across a frequency range from 0.1 Hz to 10 Hz. The calibration data further enabled the optimization of a multistage exponential smoothing model of the system that allowed the generation of arbitrary complex waveforms. This was demonstrated by combining flow modulation with a constant background flow generated by a syringe pump to mimic the pulsatile flow found in the human vascular system.

Numerical Study of the Blood Flow in a Deformable Human Aorta

In this work, we present a numerical investigation of blood flow in a portion of the human vascular system. More precisely, the present work analyzed the blood flow in the upper portion of the aorta. The aorta and its ramified blood vessels are surrounded by the cardiac muscle. The blood flow generates pressure on the internal surfaces of the artery and its ramifications, thereby causing deformation of the cardiac muscle. The numerical analysis used the Navier–Stokes equations as the governing equations of blood flow for the calculation of the velocity field and pressure distribution in the blood. The neo-Hookean hyperelastic model was used for the description of the behavior of the vessel walls. The velocity and pressure distributions were analyzed. The deformation of the vessel was also investigated. The numerical results could be used to better understand and predict the factors that trigger cardiovascular diseases and distortions of the aorta and as a diagnostic tool in clinical applications.

A 4-Chamber Model Heart with 3D Printed Silicone Aorta and Peripheral Arteries to Simulate the Human Cardiovascular System in a Mock Circulatory Loop

Purpose Mock circulatory loops (MCL) provide an in vitro platform to evaluate hemodynamic performance of cardiovascular (CV) medical devices. Designing a tunable MCL that mimics patient-specific physiology could both accelerate evaluation of medical devices prior to in vivo studies, and provide patient-specific testing in vitro. We developed an MCL that mimics human CV physiology with a 4-chamber model heart and 3D printed silicone vasculature based on patient-specific images. Methods The model heart is composed of the left/right atria & ventricles, and atrioventricular and aortic/pulmonary valves. The atrial/ventricular septa are designed as circular silicone-membranes to simulate physiologic septal deformations which occur in the native heart with a pressure differential between chambers. Each of the four chambers is made of acrylic and driven by linear motor. A displacement transducer connected to each linear motor can measure the volume change in each chamber while pressure is simultaneously recorded. A systemic vasculature model is fabricated out of 3D printed silicone based on patient-derived images. The compliance of the silicone selected is designed to match the arterial stiffness of the human vascular system. Results The assembled model heart contains atria, ventricles, and systemic vasculature. Each atrial and ventricular chamber can accommodate a maximum volume of 98 mL and 192 mL, respectively. The area and thickness of the silicone septum between the atria are 890 mm2, and 1.8 mm. The ventricular septal area and thickness are 1590 mm2 and 4.5 mm. Changes in pressure differential between the ventricular chambers affect septal configuration to incorporate ventricle-ventricle interaction effects. The linear motors are driven based on the elastance functions derived from pressure-volume (PV) loops obtained in the 4 chambers to enable the 4-chamber heart to physiologically respond to preload and afterload changes -in a similar fashion to the native heart. Conclusion This is the first MCL system that mimics human heart size, complexity and physiology and contains a human vascular circuit that can be tuned to patient-specific parameters. By including a physiologic control system governing the linear motors we can evaluate patient-specific hemodynamics, including the Frank-Starling mechanism in this MCL.

A Novel Strategy for Creating Tissue-Engineered Biomimetic Blood Vessels Using 3D Bioprinting Technology.

In this work, a novel strategy was developed to fabricate prevascularized cell-layer blood vessels in thick tissues and small-diameter blood vessel substitutes using three-dimensional (3D) bioprinting technology. These thick vascularized tissues were comprised of cells, a decellularized extracellular matrix (dECM), and a vasculature of multilevel sizes and multibranch architectures. Pluronic F127 (PF 127) was used as a sacrificial material for the formation of the vasculature through a multi-nozzle 3D bioprinting system. After printing, Pluronic F127 was removed to obtain multilevel hollow channels for the attachment of human umbilical vein endothelial cells (HUVECs). To reconstruct functional small-diameter blood vessel substitutes, a supporting scaffold (SE1700) with a double-layer circular structure was first bioprinted. Human aortic vascular smooth muscle cells (HA-VSMCs), HUVECs, and human dermal fibroblasts–neonatal (HDF-n) were separately used to form the media, intima, and adventitia through perfusion into the corresponding location of the supporting scaffold. In particular, the dECM was used as the matrix of the small-diameter blood vessel substitutes. After culture in vitro for 48 h, fluorescent images revealed that cells maintained their viability and that the samples maintained structural integrity. In addition, we analyzed the mechanical properties of the printed scaffold and found that its elastic modulus approximated that of the natural aorta. These findings demonstrate the feasibility of fabricating different kinds of vessels to imitate the structure and function of the human vascular system using 3D bioprinting technology.

Emerging trends in multiscale modeling of vascular pathophysiology: Organ-on-a-chip and 3D printing

Most biomedical and pharmaceutical research of the human vascular system aims to unravel the complex mechanisms that drive disease progression from molecular to organ levels. The knowledge gained can then be used to innovate diagnostic and treatment strategies which can ultimately be determined precisely for patients. Despite major advancements, current modeling strategies are often limited at identifying, quantifying, and dissecting specific cellular and molecular targets that regulate human vascular diseases. Therefore, development of multiscale modeling approaches are needed that can advance our knowledge and facilitate the design of next-generation therapeutic approaches in vascular diseases. This article critically reviews animal models, static in vitro systems, and dynamic in vitro culture systems currently used to model vascular diseases. A leading emphasis on the potential of emerging approaches, specifically organ-on-a-chip and three-dimensional (3D) printing, to recapitulate the innate human vascular physiology and anatomy is described. The applications of these approaches and future outlook in designing and screening novel therapeutics are also presented.

Моделирование гемодинамики сосудистых протезов «КемАнгипротез» in silico

The paper describes aspects of the application of numerical simulation of fluid flows in clinical medicine with interventions on the human vascular system. The modeling method used in the study is verified using the data of the doppler sonography of the patient underwent vascular replacement. It was shown that the deviation between the numerical experiment and the clinical data - pressure curves at the inlet and outlet of the studied vessel, is 20%. The obtained quantitative characteristics of the flow: peak systolic velocity, final diastolic velocity, minimum diastolic velocity, resistivity index, pulsatility index, systole/diastole index are comparable between verification and experimental data. Thus, for the proximal site of the clinical vessel the corresponding indices were 96.5 cm/s; 4.5 cm/s; 36.2 cm/s; 1.05; 11.5; 21.3. For simulation, 107.9 cm/s; 4.44 cm/s; 43.9 cm/s; 1.05; 12.0; 24.3. In addition, the work describes the application of tested method in two clinical vascular prostheses "KemAngioprotez" for the assessment of zones of increased shear stress and, thus, the risk of thrombus formation. It is shown that the distribution of critical zones corresponds to zones of anastomosis between prosthesis segments, which may be a potential location for optimization of the device.

Protective effects of regular physical activity on human vascular system.

Regular physical activity exerts a comprehensive beneficial effect on the human vascular system. The benefits provided by physical activity are both direct and indirect. Direct protective actions of aerobic exercise are identifiable on vascular structures and functions, since regular physical activity guarantees the integrity of the endothelial function, promotes the decrease of oxidative stress and prompts the development of new muscular capillaries. Moreover, moderate aerobic effort has positive effects on fibrinolysis, blood viscosity and vascular tone. Indirect benefits include the pleiotropic actions of physical activity on cardiovascular risk factors, in particular hypercholesterolemia, hypertension, diabetes mellitus and obesity. In a primary and secondary prevention perspective, moderate physical activity reduces in a significant way the risk of appearance of ischemic heart disease and the mortality of already established ischemic heart disease. In conclusion, health operators ought to remind their patients to "Stay physically active" in order to "Stay really fit and healthy".

Addition of the Vascular Niche Component to the Human Bone Marrow-like Scaffold Model

Previously, we have reported that our human bone marrow (BM)-like scaffold xenograft model allows the engraftment and outgrowth of normal and malignant hematopoiesis (e.g. multiple myeloma (MM), acute myelocytic/lymphocytic leukemia (AML/ALL) and MDS (Groen et al. Blood 2012; Gutierrez et al. JCI 2014 and data not shown). Whereas the presence of osteoblasts and bone of human origin mimics a human BM-like niche more closely than the murine BM in standard xenotransplant models (e.g. NOD-SCID/NSG mice), still some essential components of the human BM niche, i.e. human blood vessels, are missing. To this end, in addition to human mesenchymal stromal cells we now incorporated cord blood-derived endothelial progenitor cells (CB-EPCs) in the hybrid scaffold production process, to create a multi-tissue compartment that "maximally humanizes" the BM-like niche of our scaffolds. Towards successful implementation of a human vascular system we compared: i) scaffold material composition (biphasic calcium phosphate (BCP) vs. tricalcium phosphate (TCP)); ii) scaffold shape (particles vs. tubes); iii) different types of matrigel for CB-EPC embedding. Histological analysis of the humanized scaffolds, eight weeks after implantation in mice, showed a large number of functional human blood vessels, as indicated by hCD31+ staining and the presence of erythrocytes within. Comparison of the composition and the shapes of the scaffolds indicated superiority of TCP and tube-shaped scaffolds in supporting the formation of vessels. Further analysis of scaffolds for CD44, CD146, LEPR and nestin-positive cells, revealed the presence of other stromal niche cells besides human osteoblasts and endothelial cells. Irradiation of mice carrying these humanized implants did not have a significant deleterious effect on the established human vessels, allowing their further functional evaluation in xenotransplantation. Additionally, mice carrying tubes with and without human CB-EPC derived vessels (on either flank) were subsequently inoculated with adult BM-derived CD34-positive cells by intracardiac injection. Upon analysis 12 weeks later, all tubes showed multi-lineage hematopoietic outgrowth. Interestingly, CB-EPC embedment resulted in increased numbers of CD45+ (2-fold), CD13+ (4-fold) and CD7+ (2-fold), while CD19+ cell numbers were equal. In contrast, in mouse BM almost only CD19+ cells could be detected. Moreover, we observed that the use of CB-EPCs in our scaffolds provides faster kinetics of in vivo engraftment and growth of both patient-derived MM or AML cells. With the addition of both human CB-EPCs and human BM stromal cells, our scaffold systems now simulate both human endosteal and vascular niches of the BM, thereby more closely recapitulating the human hematopoietic niche. DisclosuresYuan:Xpand Biotechnology BV: Employment. de Bruijn:Xpand Biotechnology BV: Employment. Mitsiades:TEVA: Research Funding; Janssen/Johnson & Johnson: Research Funding; Novartis: Research Funding. Martens:Johnson & Johnson: Research Funding. Groen:Johnson & Johnson: Research Funding.

Biofunctionalization via flow shear stress resistant adhesive polysaccharide, hyaluronic acid-catechol, for enhanced in vitro endothelialization

We report a single-step method for achieving in vitro endothelialization using a water-resistant adhesive polysaccharide, hyaluronic acid (HA). Introduction of adhesive properties is inspired by the catechol chemistry utilized in marine mussels, in which bioactive hyaluronic acid is chemically modified into hyaluronic acid-catechol (HA-catechol). Quantification of cell adhesiveness to HA-catechol coated substrate was performed with microfluidic device-based adhesion assay under shear forces. The HA-catechol exhibited enhanced ability of surface binding under flow shear force condition compared to unmodified HA. HA-catechol was able to retain the adhered endothelial cells under fluid shear stresses up to 150dyn/cm2, which is above the physiological condition in human vascular system. This is the first study demonstrating utility of the adhesive force of catechol-tethered polymers under continuous shear force environments such as microfluidic devices. The HA-catechol compound developed herein could provide a straightforward strategy for improving stability in surface retention and preventing substantial tissue damage from the fluctuating blood flow after vascular reconstructive surgery.

Pharmacological therapy of age-related macular degeneration based on etiopathogenesis

It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors for the disease and are older than 50 years; (2) who have been diagnosed with unilateral age-related macular degeneration in order to prevent damage of the contralateral eye; (3) who have bilateral age-related macular degeneration in order to avert deterioration and in the hope of a potential improvement. However, randomised prospective clinical trials are still needed to elucidate the potential role of these drug treatments in the prevention and treatment of age-related macular degeneration.

Monitoring of cerebral blood flow autoregulation in adults undergoing sevoflurane anesthesia: a prospective cohort study of two age groups.

Autoregulation of blood flow is a key feature of the human cerebral vascular system to assure adequate oxygenation and metabolism of the brain under changing physiological conditions. The impact of advanced age and anesthesia on cerebral autoregulation remains unclear. The primary objective of this study was to determine the effect of sevoflurane anesthesia on cerebral autoregulation in two different age groups. This is a follow-up analysis of data acquired in a prospective observational cohort study. One hundred thirty-three patients aged 18-40 and ≥65years scheduled for major noncardiac surgery under general anesthesia were included. Cerebral autoregulation indices, limits, and ranges were compared in young and elderly patient groups. Forty-nine patients (37%) aged 18-40years and 84 patients (63%) aged ≥65years were included in the study. Age-adjusted minimum alveolar concentrations of sevoflurane were 0.89±0.07 in young and 0.99±0.14 in older subjects (P<0.001). Effective autoregulation was found in a blood pressure range of 13.8±9.8mmHg in young and 10.2±8.6mmHg in older patients (P=0.079). The lower limit of autoregulation was 66±12mmHg and 73±14mmHg in young and older patients, respectively (P=0.075). The association between sevoflurane concentrations and autoregulatory capacity was similar in both age groups. Our data suggests that the autoregulatory plateau is shortened in both young and older patients under sevoflurane anesthesia with approximately 1 MAC. Lower and upper limits of cerebral blood flow autoregulation, as well as the autoregulatory range, are not influenced by the age of anesthetized patients. Trial registration ClinicalTrials.gov (NCT00512200).

A numerical model of pulsatile blood flow in compliant arteries of a truncated vascular system

Three dimensional blood flow in compliant, tapering vessels of a truncated vascular system model containing two levels of bifurcation was investigated numerically using a commercially available finite element analysis and simulation software. Although the branching pattern and the geometry of the human vascular system are complex, they can be specified for small arteries using Murray's hypothesis that the structure of the vascular system obeys the principle of minimum work. Accordingly, in the current vascular system model, the parent/daughter diameter ratios and the angles of bifurcation were specified according to Murray's law. Another geometrical parameter, the ratio of blood vessel length to diameter, was determined according to data found in the literature. The vascular system model also includes a 5mm thick layer of tissue surrounding the vessels. This tissue layer helps to resist artery deformation during the cardiac cycle. Experimentally measured time dependent blood velocity data, available in the literature, were used as the inlet boundary condition to represent the cardiac cycle. An outflow boundary model, consisting of an elastic tube followed by a contraction tube, was used at the four outlets to represent both the compliance and the pressure drop of the small arteries, arterioles, and capillaries that would follow the truncated vascular system. The results show that, at each bifurcation, the blood flow velocity decreases significantly in the transition from the parent vessel to the daughter vessels due to the higher total cross-sectional area of the daughter vessels as compared to the parent vessel. This decrease in velocity is partially recovered along the arteries due to the tapering of the blood vessels. It can also be observed from the results that the pressure distributions and pressure drops along the vascular system are in good agreement with the physiological data found in the literature. The results also show that the velocity profiles immediately following a bifurcation are not initially symmetric, with their maxima shifted toward the inner part of the bifurcation in the daughter vessels. Finally, the results show that the maximum deformation is about 2% of the average vessel radius, which is relatively small and typical for small arteries.

The Polyphenolics and Health Effects of Pomegranate

Pomegranate (Punica granatum L.) is a useful fruit which mostly consumed as fresh fruit and can also be used as a various of processed products. Reports proved pomegranate were beneficial to health. Polyphenolic compounds in pomegranate especially ellagitannin (hydrolyzed), anthocyanins, gallotannin,and ellagic acid can maintain oral hygiene, healthy skin from the effects of free radicals caused by UV radiation, has the ability to synthesize cholesterol, destroying free radicals in the human vascular system and can prevent prostate cancer. In vitro and in vivo test has shown the fruit is acting as anti diabetic drug, and hypolipidemic, anticarcinogenic, antibacterial, anti inflamation, and antiviral. This review presenting an overview about the bioactive compound contents, physiological and health function of the fruit.

The Polyphenolics and Health Effects of Pomegranate

Pomegranate (Punica granatum L.) is a useful fruit which mostly consumed as fresh fruit and can also be used as a various of processed products. Reports proved pomegranate were beneficial to health. Polyphenolic compounds in pomegranate especially ellagitannin (hydrolyzed), anthocyanins, gallotannin,and ellagic acid can maintain oral hygiene, healthy skin from the effects of free radicals caused by UV radiation, has the ability to synthesize cholesterol, destroying free radicals in the human vascular system and can prevent prostate cancer. In vitro and in vivo test has shown the fruit is acting as anti diabetic drug, and hypolipidemic, anticarcinogenic, antibacterial, anti inflamation, and antiviral. This review presenting an overview about the bioactive compound contents, physiological and health function of the fruit.

Blood Flow Dynamics in Cerebral Aneurysm - A CFD Simulation

In the present study, the dynamics of blood flow in saccular cerebral aneurysms is investigated. The aneurysm is considered to be located at an arterial bend in human vascular system. The flow field is analyzed computationally by three-dimensional Navier-Stokes equation for laminar flow of incompressible Newtonian fluid. Circular and elliptical necks of different sizes are studied. The vascular wall is considered rigid for simplicity. Hemodynamic parameters such as velocity, pressure, vortices, wall shear stress and so on are considered for characterization of flow field. Results showed that the vortex location, inflow area in the neck and so on are varied significantly with the geometrical parameter of the aneurysm.