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1.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638793

RESUMO

Differentiation of pluripotent stem cells to cardiomyocytes is influenced by culture conditions including the extracellular matrices or similar synthetic scaffolds on which they are grown. However, the molecular mechanisms that link the scaffold with differentiation outcomes are not fully known. Here, we determined by immunofluorescence staining and mass spectrometry approaches that extracellular matrix (ECM) engagement by mouse pluripotent stem cells activates critical components of canonical wingless/integrated (Wnt) signaling pathways via kinases of the focal adhesion to drive cardiomyogenesis. These kinases were found to be differentially activated depending on type of ECM engaged. These outcomes begin to explain how varied ECM composition of in vivo tissues with development and in vitro model systems gives rise to different mature cell types, having broad practical applicability for the design of engineered tissues.


Assuntos
Diferenciação Celular , Matriz Extracelular/metabolismo , Adesões Focais/metabolismo , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , Células-Tronco Pluripotentes/metabolismo , Via de Sinalização Wnt , Animais , Camundongos
2.
J Clin Invest ; 131(17)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34623330

RESUMO

The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support contractility for the circulation. Cardiac metabolism is omnivorous, utilizing multiple substrates and metabolic pathways to produce this energy. Cardiac development, metabolic tuning, and the response to ischemia are all regulated in part by the hypoxia-inducible factors (HIFs), central components of essential signaling pathways that respond to hypoxia. Here we review the actions of HIF1, HIF2, and HIF3 in the heart, from their roles in development and metabolism to their activity in regeneration and preconditioning strategies. We also discuss recent work on the role of HIFs in atherosclerosis, the precipitating cause of myocardial ischemia and the leading cause of death in the developed world.


Assuntos
Aterosclerose/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Coração/crescimento & desenvolvimento , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Animais , Aterosclerose/etiologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Precondicionamento Isquêmico Miocárdico , Redes e Vias Metabólicas , Camundongos , Camundongos Knockout , Modelos Cardiovasculares , Isquemia Miocárdica/etiologia , Neovascularização Patológica , Neovascularização Fisiológica
3.
Hamostaseologie ; 41(5): 356-364, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34695852

RESUMO

Cardiovascular manifestations are frequent in COVID-19 infection and are predictive of adverse outcomes. Elevated cardiac biomarkers are common findings in patients with cardiovascular comorbidities and severe COVID-19 infection. Troponin, inflammatory and thrombotic markers may also improve risk prediction in COVID-19. In our comprehensive review, we provide an overview of the incidence, potential mechanisms and outcome of acute cardiac injury in COVID-19. Thereby, we discuss coagulation abnormalities in sepsis and altered immune response as contributing factors favoring myocardial injury. We further highlight the role of endothelial damage in the pathophysiological concepts. Finally, observational studies addressing the incidence of myocardial infarction during COVID-19 pandemic are discussed.


Assuntos
COVID-19/epidemiologia , Traumatismos Cardíacos/epidemiologia , Infarto do Miocárdio/epidemiologia , Pandemias , SARS-CoV-2 , Biomarcadores/sangue , COVID-19/sangue , COVID-19/mortalidade , Comorbidade , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/mortalidade , Humanos , Incidência , Modelos Cardiovasculares , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , SARS-CoV-2/patogenicidade , Troponina/sangue
4.
Sensors (Basel) ; 21(20)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34696104

RESUMO

Rotary left ventricular assist devices (LVAD) have emerged as a long-term treatment option for patients with advanced heart failure. LVADs need to maintain sufficient physiological perfusion while avoiding left ventricular myocardial damage due to suction at the LVAD inlet. To achieve these objectives, a control algorithm that utilizes a calculated suction index from measured pump flow (SIMPF) is proposed. This algorithm maintained a reference, user-defined SIMPF value, and was evaluated using an in silico model of the human circulatory system coupled to an axial or mixed flow LVAD with 5-10% uniformly distributed measurement noise added to flow sensors. Efficacy of the SIMPF algorithm was compared to a constant pump speed control strategy currently used clinically, and control algorithms proposed in the literature including differential pump speed control, left ventricular end-diastolic pressure control, mean aortic pressure control, and differential pressure control during (1) rest and exercise states; (2) rapid, eight-fold augmentation of pulmonary vascular resistance for (1); and (3) rapid change in physiologic states between rest and exercise. Maintaining SIMPF simultaneously provided sufficient physiological perfusion and avoided ventricular suction. Performance of the SIMPF algorithm was superior to the compared control strategies for both types of LVAD, demonstrating pump independence of the SIMPF algorithm.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Modelos Cardiovasculares , Sucção
5.
PLoS One ; 16(10): e0258313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34637464

RESUMO

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.


Assuntos
Poluição do Ar/análise , Arritmias Cardíacas/etiologia , Simulação por Computador , Átrios do Coração/patologia , Chumbo/efeitos adversos , Material Particulado/efeitos adversos , Potenciais de Ação/fisiologia , Poluentes Atmosféricos , Arritmias Cardíacas/fisiopatologia , Fenômenos Químicos , Átrios do Coração/fisiopatologia , Humanos , Modelos Cardiovasculares , Espectrometria por Raios X
6.
PLoS One ; 16(10): e0258225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34653194

RESUMO

BACKGROUND: Right (R) or left (L) ventricular outflow tract (VOT) obstruction can be either a dynamic phenomenon or a congenital anatomic lesion, which requires a prompt and optimal timing of treatment to avoid a pathological ventricular remodelling. OBJECTIVE: To develop a simple and reliable numerical tool able to relate the R/L obstruction size with the pressure gradient and the cardiac output. To provide indication of the obstruction severity and be of help in the clinical management of patients and designing the surgical treatment for obstruction mitigation. METHODS: Blood flow across the obstruction is described according to the classical theory of one-dimensional flow, with the obstruction uniquely characterized by its size. Hemodynamics of complete circulation is simulated according to the lumped parameter approach. The case of a 2 years-old baby is reproduced, with the occlusion placed in either the R/ or the L/VOT. Conditions from wide open to almost complete obstruction are reproduced. RESULTS: Both R/LVOT obstruction in the in-silico model resulted in an increased pressure gradient and a decreased cardiac output, proportional to the severity of the VOT obstruction and dependent on the R/L location of the obstruction itself, as it is clinically observed. CONCLUSION: The in-silico model of ventricular obstruction which simulates pressure gradient and/or cardiac output agrees with clinical data, and is a first step towards the creation of a tool that can support the clinical management of patients from diagnosis to surgical treatments.


Assuntos
Simulação por Computador , Hemodinâmica/fisiologia , Modelos Cardiovasculares , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Débito Cardíaco/fisiologia , Criança , Ventrículos do Coração/fisiopatologia , Humanos , Pressão , Artéria Pulmonar/fisiopatologia
7.
PLoS One ; 16(10): e0258047, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34597313

RESUMO

Quantification of pressure drop across stenotic arteries is a major element in the functional assessment of occlusive arterial disease. Accurate estimation of the pressure drop with a numerical model allows the calculation of Fractional Flow Reserve (FFR), which is a haemodynamic index employed for guiding coronary revascularisation. Its non-invasive evaluation would contribute to safer and cost-effective diseases management. In this work, we propose a new formulation of a reduced-order model of trans-stenotic pressure drop, based on a consistent theoretical analysis of the Navier-Stokes equation. The new formulation features a novel term that characterises the contribution of turbulence effect to pressure loss. Results from three-dimensional computational fluid dynamics (CFD) showed that the proposed model produces predictions that are significantly more accurate than the existing reduced-order models, for large and small symmetric and eccentric stenoses, covering mild to severe area reductions. FFR calculations based on the proposed model produced zero classification error for three classes comprising positive (≤ 0.75), negative (≥ 0.8) and intermediate (0.75 - 0.8) classes.


Assuntos
Constrição Patológica/fisiopatologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Modelos Cardiovasculares , Doenças Vasculares/fisiopatologia , Simulação por Computador , Hemodinâmica , Humanos , Hidrodinâmica
8.
J Int Med Res ; 49(9): 3000605211042503, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34515575

RESUMO

The effects of increasing blood flow on the pathogenic wall shear stress (pWSS) of subclavian arteries (SAs) are currently unclear. Patient-specific models of the SA were constructed based on computed tomographic images from two patients. Using the Ansys Fluent 19.0 transient laminar flow solver, the finite volume method was chosen to solve the Navier-Stokes equation governing fluid behavior. The time-averaged wall shear stress, ratio of risk area, cumulative ratio of risk area (P¯), ratio of risk time, and ratio contour of risk time were calculated to describe the temporal and spatial distributions of pWSS. Virtually all pWSS occurred during the diastolic phase. The P¯ was 2.3 and 1.29 times higher on the left than on the right in Patients 1 (P1) and 2 (P2), respectively. Increasing the blood flow volume of the left SA by 20%, 40%, and 60% led to a 9.27%, 15.10%, and 20.99% decrease in P¯ for P1 and a 5.74%, 11.55%, and 17.14% decrease in P¯ for P2, respectively, compared with baseline values. In conclusion, the left SA showed greater diastolic pWSS than the right SA, and increasing the blood flow volume reduced the pWSS in the left SA.


Assuntos
Modelos Cardiovasculares , Artéria Subclávia , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Hemodinâmica , Humanos , Estresse Mecânico , Artéria Subclávia/diagnóstico por imagem
9.
Comput Biol Med ; 137: 104830, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34534792

RESUMO

Mathematical simulations using the bidomain model, which represents cardiac tissue as consisting of an intracellular and an extracellular space, are a key approach that can be used to improve understanding of heart conditions such as ischaemia. However, key inputs to these models, such as the bidomain conductivity values, are not known with any certainty. Since efforts are underway to measure these values, it would be useful to be able to quantify the effect on model outputs of uncertainty in these inputs, and also to determine, if possible, which are the most important values to focus on in experimental studies. Our previous work has systematically studied the sensitivity of heart surface potentials to the bidomain conductivity values, and this was performed using a half-ellipsoidal model of the left ventricle. This study uses a bi-ventricular heart in a torso model and this time looks at the sensitivity of the torso surface potentials, as well as the heart surface potentials, to various conductivity values (blood, torso and the six bidomain conductivities). We found that both epicardial and torso potentials are the most sensitive to the intracellular longitudinal (along the cardiac fibres) conductivity (gil) with more minor sensitivity to the torso conductivity, and that changes in gil have a significant effect on the surface potential distributions on both the torso and the heart.


Assuntos
Modelos Cardiovasculares , Isquemia Miocárdica , Potenciais de Ação , Simulação por Computador , Condutividade Elétrica , Coração , Sistema de Condução Cardíaco , Humanos , Isquemia , Tronco
10.
Int Heart J ; 62(5): 1106-1111, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34544984

RESUMO

The proximal optimizing technique (POT) -proximal balloon edge dilation (PBED) sequence for side branch (SB) dilatation with cross-over single-stent implantation decreases both strut obstruction at the SB ostium and stent deformation at the main branch (MB).The purpose of this experimental bench test was to assess the impact of stent design on stent deformation, obstruction by stent struts at a jailed SB ostium, and stent strut malapposition in the POT-PBED sequence.Fractal coronary bifurcation bench models (60- and 80-degree angles) were used, and crossover single-stent implantation (3-link stent: XIENCE Sierra, Abbott Vascular, Santa Clara, CA, n = 10; 2-link stent: Synergy, Boston Scientific, Marlborough, MA, n = 10) was performed from the MB using the POT-PBED sequence. Jailing rates at the SB ostium, stent deformation, and stent strut malapposition of the bifurcation segment were assessed using videoscopy and optical coherence tomography.After SB dilatation using the PBED technique, jailing rates at the SB ostium and stent deformation did not differ significantly between the two types of stents. Conversely, the rate of malapposed struts of the bifurcation segment after the PBED procedure was significantly lower with 3-link stents than with 2-link stents for both 60- and 80-degree angles (60-degree angle: 4.3% ± 4.4% versus 22.0% ± 11.1%, P = 0.044; 80-degree angle: 20.8% ± 15.1% versus 57.2% ± 17.0%, P < 0.001, respectively).In the POT-PBED sequence, 3-link stents might be a preferable coronary bifurcation stent, maintaining a jailed SB ostium while significantly reducing stent strut malapposition of the bifurcation segment when compared with 2-link stents.


Assuntos
Angioplastia Coronária com Balão/métodos , Intervenção Coronária Percutânea/instrumentação , Desenho de Prótese/efeitos adversos , Stents/efeitos adversos , Angioplastia Coronária com Balão/estatística & dados numéricos , Vasos Coronários/anatomia & histologia , Humanos , Modelos Anatômicos , Modelos Cardiovasculares , Stents/estatística & dados numéricos , Stents/tendências , Tomografia de Coerência Óptica
11.
Phys Rev Lett ; 127(9): 098101, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506203

RESUMO

Cardiac fibrosis is a well-known arrhythmogenic condition which can lead to sudden cardiac death. Physically, fibrosis can be viewed as a large number of small obstacles in an excitable medium, which may create nonlinear wave turbulence or reentry. The relation between the specific texture of fibrosis and the onset of reentry is of great theoretical and practical importance. Here, we present a conceptual framework which combines functional aspects of propagation manifested as conduction blocks, with reentry wavelength and geometrical clusters of fibrosis. We formulate them into the single concept of minimal functional cluster and through extensive simulations show that it characterizes the path of reexcitation accurately, and importantly its size distribution quantitatively predicts the reentry probability for different fibrosis densities and tissue excitabilities.


Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Modelos Cardiovasculares , Miocárdio/patologia , Potenciais de Ação , Análise por Conglomerados , Fibrose/patologia , Fibrose/fisiopatologia , Humanos , Dinâmica não Linear
12.
Med Eng Phys ; 96: 81-90, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34565556

RESUMO

The aorta is a high risk region for cardiovascular disease (CVD). Haemodynamic patterns leading to CVD are not well established despite numerous experimental and numerical studies. Most overlook effects of arterial compliance and pulsatile flow. However, rigid wall assumptions can lead to overestimation of wall shear stress; a key CVD determinant. This work investigates the effect of compliance on aortic arch haemodynamics experiencing pulsatility. Rigid and compliant phantoms of the arch and brachiocephalic branch (BCA) were manufactured. Stereoscopic particle image velocimetry was used to observe velocity fields. Higher velocity magnitude was observed in the rigid BCA during acceleration. However, during deceleration, the compliant phantom experienced higher velocity. During deceleration, a low velocity region initiated and increased in size in the BCA of both phantoms with irregular shape in the compliant. At mid-deceleration, considerably larger recirculation was observed under compliance compared to rigid. Another recirculation region formed and increased in size on the inner wall of the arch in the compliant during late deceleration, but not rigid. The recirculation regions witnessed identify as high risk areas for atherosclerosis formation by a previous ex-vivo study. The results demonstrate necessity of compliance and pulsatility in haemodynamic studies to obtain highly relevant clinical outcomes.


Assuntos
Aorta Torácica , Aorta , Aorta Torácica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Modelos Cardiovasculares , Imagens de Fantasmas , Fluxo Pulsátil , Reologia
13.
Rev. bras. med. esporte ; 27(5): 509-513, July-Sept. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1288622

RESUMO

ABSTRACT Introduction: Due to various uncertain and unexpected factors in life such as diseases, natural disasters, traffic accidents, and congenital disabilities, the number and proportion of lower limb amputations are still rising for many reasons, so the research on lower limb prostheses is particularly important. Objective: This work aimed to study the relationship between altitude exercise and cardiopulmonary function. Methods: A model of abnormal changes in cardiopulmonary function was established, and then 40 plateau exercisers were selected, all of whom arrived in Tibet in March 2017. The relationship between pulmonary circulation volume and internal pressure in the chest was observed and compared. The relationship between cardiopulmonary sensory reflex and exercise (high altitude) breathing and heart rate was analyzed. A comparison of the cardiopulmonary function of subjects of different genders was implemented. Moreover, the influence of different altitudes on the subjects' cardiopulmonary function and the subjects' cardiopulmonary function changes before departure and during the first, second, and third week after departure were observed and compared. Results: I. As the pressure in the thoracic cavity increased, the subjects' pulmonary circulation blood volume gradually decreased, and the decrease was most obvious in the stage of thoracic pressure −50 to 0. II. As the cardiorespiratory reflex coefficient increased, the subjects' breathing and heart rate compensatory acceleration appeared. III. Tracking and monitoring of the subjects' cardiopulmonary indicators revealed that with the increase in altitude, the subjects' average arterial pressure, respiratory frequency, and heart rate all showed an upward trend, while the blood oxygen saturation value showed a downward trend. IV. No matter how high the altitude was, the average arterial pressure, respiratory rate, and heart rate monitored of the subjects under exercise were significantly superior to the indicator values under resting state. In contrast, the blood oxygen saturation value showed the opposite trend. V. The subjects' average arterial pressure, respiration, and heart rate in the first week were higher than other periods, but the blood oxygen saturation was relatively lower. In the second and third weeks, the changes in cardiopulmonary function were relatively smooth (all P<0.05). VI. The changes in the index of the cardiopulmonary function of subjects of different genders were small (p>0.05). Conclusion: Through modeling, the results of the plateau environment on the cardiopulmonary function of the body were made clearer, and these research data provided theoretical references for the training of the sports field in the plateau area. Level of evidence II; Therapeutic studies - investigation of treatment results.


RESUMO Contexto: devido a vários fatores incertos e inesperados da vida, como doenças, desastres naturais, acidentes de trânsito e defeitos congênitos, o número e a proporção de amputações de membros inferiores ainda estão aumentando por muitos motivos, portanto, a pesquisa sobre próteses de membros inferiores é particularmente importante. Objetivo: Este trabalho teve como objetivo estudar a relação entre o exercício em altitude e a função cardiopulmonar. Métodos: Um modelo de alterações anormais da função cardiopulmonar foi estabelecido e, em seguida, 40 praticantes de exercícios de platô foram selecionados, todos chegaram ao Tibete em março de 2017. A relação entre o volume de circulação pulmonar e a pressão interna no tórax foi observada e comparada. A relação entre o reflexo sensorial cardiopulmonar e a respiração do exercício (altitude) e a frequência cardíaca foi analisada. A comparação da função cardiopulmonar de indivíduos de diferentes gêneros foi implementada. Além disso, a influência de diferentes altitudes na função cardiopulmonar dos indivíduos e as mudanças na função cardiopulmonar dos indivíduos antes da partida e durante a primeira, segunda e terceira semanas após a partida foram observadas e comparadas. Resultados: I. À medida que a pressão na cavidade torácica aumentou, o volume de sangue da circulação pulmonar dos indivíduos diminuiu gradualmente, e a diminuição foi mais óbvia no estágio de pressão torácica −50 a 0. II. À medida que o coeficiente do reflexo cardiorrespiratório aumentou, a respiração dos indivíduos e a aceleração compensatória da frequência cardíaca apareceram. III. O rastreamento e o monitoramento dos indicadores cardiopulmonares dos indivíduos revelaram que, com o aumento da altitude, a pressão arterial média, a frequência respiratória e a frequência cardíaca dos indivíduos mostraram uma tendência ascendente, enquanto o valor de saturação de oxigênio no sangue mostrou uma tendência descendente. 4. Por mais alta que fosse a altitude, a pressão arterial média, a frequência respiratória e a frequência cardíaca monitoradas dos indivíduos em exercício foram significativamente superiores aos valores do indicador em repouso, enquanto o valor da saturação de oxigênio no sangue apresentou tendência oposta. V. A pressão arterial média, respiração e frequência cardíaca dos indivíduos na primeira semana foram maiores do que em outros períodos de tempo, mas a saturação de oxigênio no sangue foi relativamente menor. Na segunda e terceira semanas, as mudanças na função cardiopulmonar foram relativamente suaves (todos P <0,05). VI. As mudanças no índice de função cardiopulmonar de sujeitos de diferentes gêneros foram pequenas (p> 0,05). Conclusão: Por meio da modelagem, os resultados do ambiente de planalto sobre a função cardiopulmonar do corpo ficaram mais claros, e os dados dessas pesquisas forneceram referenciais teóricos para o treinamento do campo esportivo na área de planalto. Nível de evidência II; Estudos terapêuticos- investigação dos resultados do tratamento.


resumen está disponible en el texto completo


Assuntos
Humanos , Masculino , Feminino , Adulto , Exercício Físico/fisiologia , Simulação/métodos , Teste de Esforço , Altitude , Modelos Cardiovasculares
14.
J Mech Behav Biomed Mater ; 123: 104745, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34482092

RESUMO

Currently, the most common replacement heart valve design is the 'bioprosthetic' heart valve (BHV), which has important advantages in that it does not require permanent anti-coagulation therapy, operates noiselessly, and has blood flow characteristics similar to the native valve. BHVs are typically fabricated from glutaraldehyde-crosslinked pericardial xenograft tissue biomaterials (XTBs) attached to a rigid, semi-flexible, or fully collapsible stent in the case of the increasingly popular transcutaneous aortic valve replacement (TAVR). While current TAVR assessments are positive, clinical results to date are generally limited to <2 years. Since TAVR leaflets are constructed using thinner XTBs, their mechanical demands are substantially greater than surgical BHV due to the increased stresses during in vivo operation, potentially resulting in decreased durability. Given the functional complexity of heart valve operation, in-silico predictive simulations clearly have potential to greatly improve the TAVR development process. As such simulations must start with accurate material models, we have developed a novel time-evolving constitutive model for pericardial xenograft tissue biomaterials (XTB) utilized in BHV (doi: 10.1016/j.jmbbm.2017.07.013). This model was able to simulate the observed tissue plasticity effects that occur in approximately in the first two years of in vivo function (50 million cycles). In the present work, we implemented this model into a complete simulation pipeline to predict the BHV time evolving geometry to 50 million cycles. The pipeline was implemented within an isogeometric finite element formulation that directly integrated our established BHV NURBS-based geometry (doi: 10.1007/s00466-015-1166-x). Simulations of successive loading cycles indicated continual changes in leaflet shape, as indicated by spatially varying increases in leaflet curvature. While the simulation model assumed an initial uniform fiber orientation distribution, anisotropic regional changes in leaflet tissue plastic strain induced a complex changes in regional fiber orientation. We have previously noted in our time-evolving constitutive model that the increases in collagen fiber recruitment with cyclic loading placed an upper bound on plastic strain levels. This effect was manifested by restricting further changes in leaflet geometry past 50 million cycles. Such phenomena was accurately captured in the valve-level simulations due to the use of a tissue-level structural-based modeling approach. Changes in basic leaflet dimensions agreed well with extant experimental studies. As a whole, the results of the present study indicate the complexity of BHV responses to cyclic loading, including changes in leaflet shape and internal fibrous structure. It should be noted that the later effect also influences changes in local mechanical behavior (i.e. changes in leaflet anisotropic tissue stress-strain relationship) due to internal fibrous structure resulting from plastic strains. Such mechanism-based simulations can help pave the way towards the application of sophisticated simulation technologies in the development of replacement heart valve technology.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Valva Aórtica , Modelos Cardiovasculares , Pericárdio , Estresse Mecânico
15.
ASAIO J ; 67(10): 1148-1158, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582408

RESUMO

Computational fluid dynamics find widespread application in the development of rotary blood pumps (RBPs). Yet, corresponding simulations rely on shear stress computations that are afflicted with limited resolution while lacking validation. This study aimed at the experimental validation of integral hydraulic properties to analyze global shear stress resolution across the operational range of a novel RBP. Pressure head and impeller torque were numerically predicted based on Unsteady Reynolds-averaged Navier-Stokes (URANS) simulations and validated on a testbench with integrated sensor modalities (flow, pressure, and torque). Validation was performed by linear regression and Bland-Altman analysis across nine operating conditions. In power loss analysis (PLA), in silico hydraulic power losses were derived based on the validated hydraulic quantities and balanced with in silico shear-dependent dissipative power losses. Discrepancies among both terms provided a measure of in silico shear stress resolution. In silico and in vitro data correlated with low discordance in pressure (r = 0.992, RMSE = 1.02 mmHg), torque (r = 0.999, RMSE = 0.034 mNm), and hydraulic power losses (r = 0.990, RMSE = 0.015W). PLA revealed numerically predicted dissipative losses to be up to 34.4% smaller than validated computations of hydraulic losses. This study confirmed the suitability of URANS settings to predict integral hydraulic properties. However, numerical credibility was hampered by lacking resolution of shear-dependent dissipative losses.


Assuntos
Coração Auxiliar , Simulação por Computador , Hidrodinâmica , Modelos Cardiovasculares , Estresse Mecânico
16.
Int J Mol Sci ; 22(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34502423

RESUMO

The adult human heart can only adapt to heart diseases by starting a myocardial remodeling process to compensate for the loss of functional cardiomyocytes, which ultimately develop into heart failure. In recent decades, the evolution of new strategies to regenerate the injured myocardium based on cellular reprogramming represents a revolutionary new paradigm for cardiac repair by targeting some key signaling molecules governing cardiac cell fate plasticity. While the indirect reprogramming routes require an in vitro engineered 3D tissue to be transplanted in vivo, the direct cardiac reprogramming would allow the administration of reprogramming factors directly in situ, thus holding great potential as in vivo treatment for clinical applications. In this framework, cellular reprogramming in partnership with nanotechnologies and bioengineering will offer new perspectives in the field of cardiovascular research for disease modeling, drug screening, and tissue engineering applications. In this review, we will summarize the recent progress in developing innovative therapeutic strategies based on manipulating cardiac cell fate plasticity in combination with bioengineering and nanotechnology-based approaches for targeting the failing heart.


Assuntos
Diferenciação Celular , Reprogramação Celular , Modelos Cardiovasculares , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Regeneração , Animais , Humanos
17.
Int J Artif Organs ; 44(11): 793-806, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34581613

RESUMO

Heart failure is a major health risk, and with limited availability of donor organs, there is an increasing need for developing cardiac assist devices (CADs). Mock circulatory loops (MCL) are an important in-vitro test platform for CAD's performance assessment and optimisation. The MCL is a lumped parameter model constructed out of hydraulic and mechanical components aiming to simulate the native cardiovascular system (CVS) as closely as possible. Further development merged MCLs and numerical circulatory models to improve flexibility and accuracy of the system; commonly known as hybrid MCLs. A total of 128 MCLs were identified in a literature research until 25 September 2020. It was found that the complexity of the MCLs rose over the years, recent MCLs are not only capable of mimicking the healthy and pathological conditions, but also implemented cerebral, renal and coronary circulations and autoregulatory responses. Moreover, the development of anatomical models made flow visualisation studies possible. Mechanical MCLs showed excellent controllability and repeatability, however, often the CVS was overly simplified or lacked autoregulatory responses. In numerical MCLs the CVS is represented with a higher order of lumped parameters compared to mechanical test rigs, however, complex physiological aspects are often simplified. In hybrid MCLs complex physiological aspects are implemented in the hydraulic part of the system, whilst the numerical model represents parts of the CVS that are too difficult to represent by mechanical components per se. This review aims to describe the advances, limitations and future directions of the three types of MCLs.


Assuntos
Sistema Cardiovascular , Coração Auxiliar , Coração , Hemodinâmica , Modelos Cardiovasculares
18.
Comput Methods Biomech Biomed Engin ; 24(15): 1718-1729, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34569360

RESUMO

PURPOSE: The flow velocity of visceral arteries was measured by 2D PCMRI to produce the patient-specific flow BC imposed on the outlets of visceral arteries in CFD simulation. This modified method aimed to improve the CFD accuracy in the abdominal aorta and visceral arteries. METHODS: A volunteer underwent non-contrast-enhanced MRA to scan the abdominal aorta and visceral arteries, and 2D PCMRI to obtain the flow velocity of the aforementioned vessels. The three-dimensional geometric model was reconstructed using the MRI scan data of the abdominal aorta and visceral arteries. The flow waveforms measured by 2D PCMRI were processed and then imposed on the aortic inlet and the outlets of all visceral arteries as the flow BC. The RCR parameters of the three elements Windkessel model were modulated and imposed on the aortic outlet. CFD simulation was run in the open-source software: svSolver. The same volunteer underwent 4D flow MRI to compare the flow field with those extracted from CFD results. RESULTS: Four specific time points in a cardiac cycle and three cross-sectional planes of aorta were selected to analyze the flow field, pressure and wall shear stress (WSS) from CFD. The flow waveforms and streamlines of CFD agreed with those of 4D flow MRI. The pressure waveforms, pressure distribution and WSS distribution from CFD conformed with the physiological condition of human body. CONCLUSION: These results suggest this modified CFD method may yield reasonable flow field, pressure and WSS in the abdominal aorta and visceral arteries.


Assuntos
Aorta Abdominal , Hidrodinâmica , Aorta Abdominal/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Simulação por Computador , Estudos Transversais , Hemodinâmica , Humanos , Modelos Cardiovasculares
19.
Int Rev Cell Mol Biol ; 363: 203-269, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34392930

RESUMO

An increase in intracellular Ca2+ concentration ([Ca2+]i) regulates a plethora of functions in the cardiovascular (CV) system, including contraction in cardiomyocytes and vascular smooth muscle cells (VSMCs), and angiogenesis in vascular endothelial cells and endothelial colony forming cells. The sarco/endoplasmic reticulum (SR/ER) represents the largest endogenous Ca2+ store, which releases Ca2+ through ryanodine receptors (RyRs) and/or inositol-1,4,5-trisphosphate receptors (InsP3Rs) upon extracellular stimulation. The acidic vesicles of the endolysosomal (EL) compartment represent an additional endogenous Ca2+ store, which is targeted by several second messengers, including nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], and may release intraluminal Ca2+ through multiple Ca2+ permeable channels, including two-pore channels 1 and 2 (TPC1-2) and Transient Receptor Potential Mucolipin 1 (TRPML1). Herein, we discuss the emerging, pathophysiological role of EL Ca2+ signaling in the CV system. We describe the role of cardiac TPCs in ß-adrenoceptor stimulation, arrhythmia, hypertrophy, and ischemia-reperfusion injury. We then illustrate the role of EL Ca2+ signaling in VSMCs, where TPCs promote vasoconstriction and contribute to pulmonary artery hypertension and atherosclerosis, whereas TRPML1 sustains vasodilation and is also involved in atherosclerosis. Subsequently, we describe the mechanisms whereby endothelial TPCs promote vasodilation, contribute to neurovascular coupling in the brain and stimulate angiogenesis and vasculogenesis. Finally, we discuss about the possibility to target TPCs, which are likely to mediate CV cell infection by the Severe Acute Respiratory Disease-Coronavirus-2, with Food and Drug Administration-approved drugs to alleviate the detrimental effects of Coronavirus Disease-19 on the CV system.


Assuntos
COVID-19/complicações , COVID-19/tratamento farmacológico , Sinalização do Cálcio/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Sistema Cardiovascular/metabolismo , Lisossomos/metabolismo , SARS-CoV-2 , ADP-Ribosil Ciclase 1/metabolismo , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , COVID-19/metabolismo , Canais de Cálcio/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Retículo Endoplasmático/metabolismo , Células Endoteliais/metabolismo , Humanos , Modelos Cardiovasculares , Miócitos Cardíacos/metabolismo , NADP/análogos & derivados , NADP/metabolismo , Receptores Adrenérgicos beta/metabolismo , Retículo Sarcoplasmático/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo
20.
Chaos ; 31(7): 073137, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34340346

RESUMO

Arrhythmogenic early afterdepolarizations (EADs) are investigated in a biophysically detailed mathematical model of a rabbit ventricular myocyte, providing their location in the parameter phase space and describing their dynamical mechanisms. Simulations using the Sato model, defined by 27 state variables and 177 parameters, are conducted to generate electrical action potentials (APs) for different values of the pacing cycle length and other parameters related to sodium and calcium concentrations. A detailed study of the different AP patterns with or without EADs is carried out, showing the presence of a high variety of temporal AP configurations with chaotic and quasiperiodic behaviors. Regions of bistability are identified and, importantly, linked to transitions between different behaviors. Using sweeping techniques, one-, two-, and three-parameter phase spaces are provided, allowing ascertainment of the role of the selected parameters as well as location of the transition regions. A Devil's staircase, with symbolic sequence analysis, is proposed to describe transitions in the ratio between the number of voltage (EAD and AP) peaks and the number of APs. To conclude, the obtained results are linked to recent studies for low-dimensional models and a conjecture is made for the internal dynamical structure of the transition region from non-EAD to EAD behavior using fold and cusp bifurcations and maximal canards.


Assuntos
Modelos Cardiovasculares , Miócitos Cardíacos , Potenciais de Ação , Animais , Arritmias Cardíacas , Cálcio , Coelhos
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