Influence of dilated cardiomyopathy and a left ventricular assist device on vortex dynamics in the left ventricle

Together with new developments in mechanical cardiac support, the analysis of vortex dynamics in the left ventricle has become an increasingly important topic in literature. The aim of this study was to develop a method to investigate the influence of a left ventricular assist device (LVAD) on vortex dynamics in a failing ventricle. An axisymmetric fluid dynamics model of the left ventricle was developed and coupled to a lumped parameter model of the complete circulation. Simulations were performed for healthy conditions and dilated cardiomyopathy (DCM). Vortex structures in these simulations were analysed by means of automated detection. Results show that the strength of the leading vortex ring is lower in a DCM ventricle than in a healthy ventricle. The LVAD further influences the maximum strength of the vortex and also causes the vortex to disappear earlier in time with increasing LVAD flows. Understanding these phenomena by means of the method proposed in this study will contribute to enhanced diagnostics and monitoring during cardiac support.     

Differential expression profiles of plasma exosomal microRNAs in dilated cardiomyopathy with chronic heart failure

As one of the most prevalent heritable cardiovascular diseases, dilated cardiomyopathy (DCM) induces cardiac insufficiency and dysfunction. Although genetic mutation has been identified one of the causes of DCM, the usage of genetic biomarkers such as RNAs for DCM early diagnosis is still being overlooked. In addition, the alternation of RNAs could reflect the progression of the diseases, as an indicator for the prognosis of patients. Therefore, it is beneficial to develop genetic based diagnostic tool for DCM. RNAs are often unstable within circulatory system, leading to the infeasibility for clinical application. Recently discovered exosomal miRNAs have the stability that is then need for diagnostic purpose. Hence, fully understanding of the exosomal miRNA within DCM patients is vital for clinical translation. In this study, we employed the next generation sequencing based on the plasma exosomal miRNAs to comprehensively characterize the miRNAs expression in plasma exosomes from DCM patients exhibiting chronic heart failure (CHF) compared to healthy individuals. A complex landscape of differential miRNAs and target genes in DCM with CHF patients were identified. More importantly, we discovered that 92 differentially expressed miRNAs in DCM patients undergoing CHF were correlated with several enriched pathways, including oxytocin signalling pathway, circadian entrainment, hippo signalling pathway-multiple species, ras signalling pathway and morphine addiction. This study reveals the miRNA expression profiles in plasma exosomes in DCM patients with CHF, and further reveal their potential roles in the pathogenesis of it, presenting a new direction for clinical diagnosis and management of DCM patients with CHF.     

Influence of dilated cardiomyopathy and a left ventricular assist device on vortex dynamics in the left ventricle

Together with new developments in mechanical cardiac support, the analysis of vortex dynamics in the left ventricle has become an increasingly important topic in literature. The aim of this study was to develop a method to investigate the influence of a left ventricular assist device (LVAD) on vortex dynamics in a failing ventricle. An axisymmetric fluid dynamics model of the left ventricle was developed and coupled to a lumped parameter model of the complete circulation. Simulations were performed for healthy conditions and dilated cardiomyopathy (DCM). Vortex structures in these simulations were analysed by means of automated detection. Results show that the strength of the leading vortex ring is lower in a DCM ventricle than in a healthy ventricle. The LVAD further influences the maximum strength of the vortex and also causes the vortex to disappear earlier in time with increasing LVAD flows. Understanding these phenomena by means of the method proposed in this study will contribute to enhanced diagnostics and monitoring during cardiac support.     

Numerical simulation of blood flow in the left ventricle and aortic sinus using magnetic resonance imaging and computational fluid dynamics

Understanding cardiac blood flow patterns has many applications in analysing haemodynamics and for the clinical assessment of heart function. In this study, numerical simulations of blood flow in a patient-specific anatomical model of the left ventricle (LV) and the aortic sinus are presented. The realistic 3D geometry of both LV and aortic sinus is extracted from the processing of magnetic resonance imaging (MRI). Furthermore, motion of inner walls of LV and aortic sinus is obtained from cine-MR image analysis and is used as a constraint to a numerical computational fluid dynamics (CFD) model based on the moving boundary approach. Arbitrary Lagrangian–Eulerian finite element method formulation is used for the numerical solution of the transient dynamic equations of the fluid domain. Simulation results include detailed flow characteristics such as velocity, pressure and wall shear stress for the whole domain. The aortic outflow is compared with data obtained by phase-contrast MRI. Good agreement was found between simulation results and these measurements.     

Effect of inlet velocity profiles on patient-specific computational fluid dynamics simulations of the carotid bifurcation

Patient-specific computational fluid dynamics (CFD) is a powerful tool for researching the role of blood flow in disease processes. Modern clinical imaging technology such as MRI and CT can provide high resolution information about vessel geometry, but in many situations, patient-specific inlet velocity information is not available. In these situations, a simplified velocity profile must be selected. We studied how idealized inlet velocity profiles (blunt, parabolic, and Womersley flow) affect patient-specific CFD results when compared to simulations employing a "reference standard" of the patient's own measured velocity profile in the carotid bifurcation. To place the magnitude of these effects in context, we also investigated the effect of geometry and the use of subject-specific flow waveform on the CFD results. We quantified these differences by examining the pointwise percent error of the mean wall shear stress (WSS) and the oscillatory shear index (OSI) and by computing the intra-class correlation coefficient (ICC) between axial profiles of the mean WSS and OSI in the internal carotid artery bulb. The parabolic inlet velocity profile produced the most similar mean WSS and OSI to simulations employing the real patient-specific inlet velocity profile. However, anatomic variation in vessel geometry and the use of a nonpatient-specific flow waveform both affected the WSS and OSI results more than did the choice of inlet velocity profile. Although careful selection of boundary conditions is essential for all CFD analysis, accurate patient-specific geometry reconstruction and measurement of vessel flow rate waveform are more important than the choice of velocity profile. A parabolic velocity profile provided results most similar to the patient-specific velocity profile.     

Beneficial effects of edaravone, a novel antioxidant, in rats with dilated cardiomyopathy

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47(phox), p67(phox), gp91(phox) and Nox4), fibrosis markers (TGF-β(1) and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis.     

Vertical profiles of current velocity and dissolved oxygen saturation in biofilms on artificial and natural substrates

We determined vertical changes in current velocity and dissolved oxygen concentration in biofilms on artificial and natural substrates using microelectrodes. We used biofilms developed on glass slides dipped in an artificial stream for 3 months, artificial clay tiles dipped in an outdoor artificial stream for 3 months, and natural pebbles. In the biofilm on a glass slide, current velocity significantly decreased from the surface of the biofilm and became 0 cm s⁻¹ at the surface of the glass slide. Vertical profile of current velocity versus depth indicated a presence of a viscous sublayer of 0.2-mm thickness above the surface of glass slide. Dissolved oxygen (DO) concentration increased within the biofilm and attained the maximum (123%) at the surface of the glass slide, indicating active photosynthesis by sessile diatoms at the layer corresponding to the observed viscous sublayer. In the biofilm on an artificial tile, DO increased to 163% saturation at 24.849-mm depth, followed by rapid decrease (6%) at the surface of the tile. A similar result of remarkable decrease in DO saturation was also found in the biofilm on a natural pebble. These results suggest that smoothness of the substrate surface is related to the vertical profile of DO saturation. The thickness of the viscous sublayer and oxygen-depleted area (up to several hundred micrometers, μm) was sufficient for the presence of bacteria, protists, and other metazoan animals, suggesting high activity and diversity of those heterotrophs in the bottom part of biofilms.     

Transcriptome analysis uncovers the autophagy‐mediated regulatory patterns of the immune microenvironment in dilated cardiomyopathy

The relationship between autophagy and immunity has been well studied. However, little is known about the role of autophagy in the immune microenvironment during the progression of dilated cardiomyopathy (DCM). Therefore, this study aims to uncover the effect of autophagy on the immune microenvironment in the context of DCM. By investigating the autophagy gene expression differences between healthy donors and DCM samples, 23 dysregulated autophagy genes were identified. Using a series of bioinformatics methods, 13 DCM‐related autophagy genes were screened and used to construct a risk prediction model, which can well distinguish DCM and healthy samples. Then, the connections between autophagy and immune responses including infiltrated immunocytes, immune reaction gene‐sets and human leukocyte antigen (HLA) genes were systematically evaluated. In addition, two autophagy‐mediated expression patterns in DCM were determined via the unsupervised consensus clustering analysis, and the immune characteristics of different patterns were revealed. In conclusion, our study revealed the strong effect of autophagy on the DCM immune microenvironment and provided new insights to understand the pathogenesis and treatment of DCM.     

Cardiac protein changes in ischaemic and dilated cardiomyopathy: a proteomic study of human left ventricular tissue

The development of heart failure (HF) is characterized by progressive alteration of left ventricle structure and function. Previous works on proteomic analysis in cardiac tissue from patients with HF remain scant. The purpose of our study was to use a proteomic approach to investigate variations in protein expression of left ventricle tissue from patients with ischaemic (ICM) and dilated cardiomyopathy (DCM). Twenty-four explanted human hearts, 12 from patients with ICM and 12 with DCM undergoing cardiac transplantation and six non-diseased donor hearts (CNT) were analysed by 2DE. Proteins of interest were identified by mass spectrometry and validated by Western blotting and immunofluorescence. We encountered 35 differentially regulated spots in the comparison CNT versus ICM, 33 in CNT versus DCM, and 34 in ICM versus DCM. We identified glyceraldehyde 3-phophate dehydrogenase up-regulation in both ICM and DCM, and alpha-crystallin B down-regulation in both ICM and DCM. Heat shock 70 protein 1 was up-regulated only in ICM. Ten of the eleven differentially regulated proteins common to both aetiologies are interconnected as a part of a same network. In summary, we have shown by proteomics analysis that HF is associated with changes in proteins involved in the cellular stress response, respiratory chain and cardiac metabolism. Although we found altered expression of eleven proteins common to both ischaemic and dilated aetiology, we also observed different proteins altered in both groups. Furthermore, we obtained that seven of these eleven proteins are involved in cell death and apoptosis processes, and therefore in HF progression.     

Effect of turbulent models on left ventricle diastolic flow patterns simulation

Abstract

Vortex structures, as one of the most important features of cardiac flow, have a crucial impact on the left ventricle function and pathological conditions. These swirling flows are closely related to the presence of turbulence in left ventricle which is investigated in the current study. Using an extended model of the left heart, including a fluid-structure interaction (FSI) model of the mitral valve with a realistic geometry, the effect of using two numerical turbulent models, k-ε and Spalart-Allmaras (SA), on diastolic flow patterns is studied and compared with results from laminar flow model. As a result of the higher dissipation rate in turbulent models (k-ε and SA), vortices are larger and stronger in the laminar flow model. Comparing E/A ratio in the three models (Laminar, k-ε, and SA) with experimental data from healthy subjects, it is concluded that the results from k-ε model are more accurate.     

A numerical analysis of the aortic blood flow pattern during pulsed cardiopulmonary bypass

In the modern era, stroke remains a main cause of morbidity after cardiac surgery despite continuing improvements in the cardiopulmonary bypass (CPB) techniques. The aim of the current work was to numerically investigate the blood flow in aorta and epiaortic vessels during standard and pulsed CPB, obtained with the intra-aortic balloon pump (IABP). A multi-scale model, realized coupling a 3D computational fluid dynamics study with a 0D model, was developed and validated with in vivo data. The presence of IABP improved the flow pattern directed towards the epiaortic vessels with a mean flow increase of 6.3% and reduced flow vorticity.     

The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy

As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy.     

The calcium release-activated calcium channel Orai1 represents a crucial component in hypertrophic compensation and the development of dilated cardiomyopathy

As exceptionally calcium selective store-operated channels, Orai channels play a prominent role in cellular calcium signaling. While most studied in the immune system, we are beginning to recognize that Orai1 provides unique calcium signaling pathways in numerous tissue contexts. To assess the involvement of Orai1 in cardiac hypertrophy we used transverse aortic constriction to model pressure overload cardiac hypertrophy and heart failure in Orai1 deficient mice. We demonstrate that Orai1 deficient mice have significantly decreased survival in this pressure overload model. Transthoracic echocardiography reveals that Orai1 deficient mice develop rapid dilated cardiomyopathy, with greater loss of function, and histological and molecular data indicate that this pathology is associated with significant apoptosis, but not major differences in cellular hypertrophy, fibrosis, and some major hypertrophic makers. Orai1 represents a crucial calcium entry mechanism in the compensation of the heart to pressure overload over-load, and the development of dilated cardiomyopathy.     

Torsional motion of the left ventricle does not affect ventricular fluid dynamics of both foetal and adult hearts

Left ventricular torsion is caused by shortening and relaxation of the helical fibres in the myocardium, and is thought to be an optimal configuration for minimizing myocardial tissue strains. Characteristics of torsional motion has also been proposed to be markers for cardiac dysfunction. However, its effects on fluid and energy dynamics in the left ventricle have not been comprehensively investigated. To investigate this, we performed image-based flow simulations on five healthy adult porcine and two healthy human foetal left ventricles (representing two different length scales) at different degrees of torsional motions. In the adult porcine ventricles, cardiac features such as papillary muscles and mitral valves, and cardiac conditions such as myocardial infarctions, were also included to investigate the effect of twist. The results showed that, for all conditions investigated, ventricular torsional motion caused minimal changes to flow patterns, and consistently accounted for less than 2% of the energy losses, wall shear stresses, and ejection momentum energy. In contrast, physiological characteristics such as chamber size, stroke volume and heart rate had a much greater influence on flow patterns and energy dynamics. The results thus suggested that it might not be necessary to model the torsional motion to study the flow and energy dynamics in left ventricles.     

Simulation of Fluid Flow in a Channel Induced by Three Types of Fin-Like Motion

One of many interesting research activities in biofluidmechanics is dedicated to investigations of locomotion in water. Some of propulsion mechanisms observed in the underwater world are used in the development process of underwater autonomic vehicles （AUV）. In order to characterise several solutions according to their manoeuvrability, influence on the surrounding fluid and energetic efficiency, a detailed analysis of fin-like movement is indispensable. In the current paper an analysis of undulatory, oscillatory and combined fin-like movements by means of numerical simulation is carried out. The conservation equation of mass and the conservation equation of momentum axe solved with the Finite Volume Method （FWM） by use of the software CFX-10.0. The undulatory and oscillatory fin movements axe modelled with an equation that is implemented within an additional subroutine and joined with the main solver. N carried out in the computational domain, in which one fin is fixed in a flow-through water duct. Simulations axe carded out in the range of the Re number up to 105. The results show significant influence of applied fin motion on the velocity distribution in the surrounding fluid.     

Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: a micro-CT based model

Natural cartilage remodels both in vivo and in vitro in response to mechanical stresses, hence mechanical stimulation is believed to be a potential tool to modulate extra-cellular matrix synthesis in tissue-engineered cartilage. Fluid-induced shear is known to enhance chondrogenesis in engineered cartilage constructs. The quantification of the hydrodynamic environment is a condition required to study the biochemical response to shear of 3D engineered cell systems. We developed a computational model of culture medium flow through the microstructure of a porous scaffold, during direct- perfused culture. The 3D solid model of the scaffold micro-geometry was reconstructed from 250 micro-computed tomography (micro-CT) images. The results of the fluid dynamic simulations were analyzed at the central portions of the fluid domain, to avoid boundary effects. The average, median and mode shear stress values calculated at the scaffold walls were 3.48, 2.90, and 2.45 mPa respectively, at a flow rate of 0.5 cm(3)/min, perfused through a 15 mm diameter scaffold, at an inlet fluid velocity of 53 microm/s. These results were compared to results estimated using a simplified micro-scale model and to results estimated using an analytical macro-scale porous model. The predictions given by the CT-based model are being used in conjunction with an experimental bioreactor model, in order to quantify the effects of fluid-dynamic shear on the growth modulation of tissue-engineered cartilage constructs, to potentially enhance tissue growth in vitro.     

The impact of arm-crank position on the drag of a paralympic hand-cyclist

The aerodynamic features associated with the rotation of a cyclist’s legs have long been a research topic for sport scientists and engineers, with studies in recent years shedding new light on the flow structures and drag trends. While the arm-crank rotation cycle of a hand-cyclist bears some resemblance to the leg rotation of a traditional cyclist, the aerodynamics around the athlete are fundamentally different due to the proximity and position of the athlete’s torso with respect to their arms, especially since both arm-cranks move in phase with each other. This research investigates the impact of arm-crank position on the drag acting on a hand-cyclist and is applied to a hill descent position where the athlete is not pedalling. Four primary arm-crank positions, namely 3, 6, 9, and 12 o’clock of a Paralympic hand-cyclist were investigated with CFD for five yaw angles, namely 0°, 5°, 10°, 15°, and 20°. The results demonstrated that the 3 and 12 o’clock positions (when observed from the left side of the hand-cyclist) yielded the highest drag area at 0° yaw, while the 9 o’clock position yielded the lowest drag area for all yaw angles. This is in contrast to the 6 o’clock position traditionally held by hand-cyclists during a descent to reduce aerodynamic drag.     

Concentrations of myosin-activating protein kinases in the myocardium of patients with dilated cardiomyopathy and in animal heart

Skeletal myosin light chain kinase in the myocardia of various animal species was identified by immunoblotting. The myocardial concentrations of this protein and myosin-activating protein kinases (RhoA-activated kinase, integrin-linked kinase, and zipper-interacting kinase) were compared in healthy humans and patients with dilated cardiomyopathy. Skeletal myosin light chain kinase was detected in the human and chicken embryo hearts, rather than in the embryonic and adult rat hearts. In the myocardium of patients with dilated cardiomyopathy, the concentrations of myosin light chain kinase, RhoA-activated kinase, and integrin-linked kinase increase and the concentration of zipper-interacting kinase decreases. The results obtained are likely to characterize compensatory processes in cardiomyocytes in dilated cardiomyopathy that are aimed at increasing their viability and contractility.