23 research outputs found
Impact of thrombus composition on virtual thrombectomy procedures using human clot analogues mechanical data
No full textEndovascular thrombectomy (EVT) aims at restoring blood flow in case of acute ischemic stroke by removing the thrombus occluding a large cerebral artery. During the procedure with stent-retriever, the thrombus is captured within the device, which is then retrieved, subjecting the thrombus to several forces, potentially leading to its fragmentation. In silico studies, along with mechanical characterisation of thrombi, can enhance our understanding of the EVT, helping the development of new devices and interventional strategies. Our group previously validated a numerical approach to study EVT able to account for thrombus fragmentation. In this study, the same methodology was employed to explore the applicability of the chosen failure criterion to EVT simulations and the impact of thrombus composition on the outcome of the in silico procedure. For the first time, human clot analogues experimental data were applied to this methodology. Clot analogues of three different compositions were tested, and a material model incorporating failure was calibrated, followed by a verification analysis. Finally, the calibrated material model was used to perform EVT simulations, combining the three tested thrombus compositions with three different stent retriever models. The experimental tests confirmed a compression-tension asymmetry in the stress-strain curves, showing decreasing stiffness with increasing the red blood cell (RBC) content. Applying the resulting material models to EVT simulations demonstrated: (i) the dependency of the failure criterion on the thrombus mesh size, (ii) a greater tendency for RBC-rich thrombi to fragment, and (iii) increased difficulty in retrieving RBC-poor thrombi compared to RBC-rich thrombi.</p
Femoral artery hemodynamics: state of the art of computational analyses and future trends
No full textFemoropopliteal artery (FPA), characterized by a unique extension and curvature, is often affected by atherosclerotic occlusive diseases, such as peripheral artery disease (PAD). The clinical trend for the treatment of the FPA has shown that none of the endovascular nor surgical treatments typically adopted for other vascular regions, including carotids and coronary arteries, provides a drawback-free follow-up. In particular, the mini-invasive approach is typically affected by restenosis and widely influenced by the environmental biomechanics of the FPA surrounding tissues. As it has been long known for other vascular districts, abnormal hemodynamics may be an important factor in driving the plaque development and restenosis in FPA. The tools to locally analyse hemodynamics in FPA are mainly computer-based; it means that the analyses are carried out by means of numerical simulations, like computational fluid dynamics (CFD) or fluid-structure interaction simulations. These analyses allow the assessment of the local distribution of hemodynamic descriptors according to the geometrical model under consideration. In this context, this short review gives insights on the main works on hemodynamic modelling of FPA, including an overview of the on-going work of our research group on this topic. Future perspectives are also provided with focus on computational models of FPA that take into account the impact of lower limb movement on hemodynamics and agent-based modelling coupled with CFD to inquire the cellular events
A response surface optimization approach to adjust ionic current conductances of cardiac electrophysiological models. Application to the study of potassium level changes.
No full textCardiac electrophysiological computational models are often developed from previously published models. The new models may incorporate additional features to adapt the model to a different species or may upgrade a specific ionic formulation based on newly available experimental data. A relevant challenge in the development of a new model is the estimation of certain ionic current conductances that cannot be reliably identified from experiments. A common strategy to estimate those conductances is by means of constrained non-linear least-squares optimization. In this work, a novel methodology is proposed for estimation of ionic current conductances of cardiac electrophysiological models by using a response surface approximation-based constrained optimization with trust region management. Polynomial response surfaces of a number of electrophysiological markers were built using statistical sampling methods. These markers included action potential duration (APD), triangulation, diastolic and systolic intracellular calcium concentration, and time constants of APD rate adaptation. The proposed methodology was applied to update the Carro et al. human ventricular action potential model after incorporation of intracellular potassium ([K+]i) dynamics. While the Carro et al. model was well suited for investigation of arrhythmogenesis, it did not allow simulation of [K+]i changes. With the methodology proposed in this study, the updated Carro et al. human ventricular model could be used to simulate [K+]i changes in response to varying extracellular potassium ([K+]o) levels. Additionally, it rendered values of evaluated electrophysiological markers within physiologically plausible ranges. The optimal values of ionic current conductances in the updated model were found in a notably shorter time than with previously proposed methodologies. As a conclusion, the response surface optimization-based approach proposed in this study allows estimating ionic current conductances of cardiac electrophysiological computational models while guaranteeing replication of key electrophysiological features and with an important reduction in computational cost with respect to previously published approaches. The updated Carro et al. model developed in this study is thus suitable for the investigation of arrhythmic risk-related conditions, including those involving large changes in potassium concentration
An In-Silico Study into the Impact of Electrophysiological Variability at the Cellular Level on the Re-entry Patterns in Atrial Fibrillation
No full textModelling the atria in-silico has become an important method in understanding atrial behaviour. Atrial models typically include regional electrophysiological variability, but neglect cellular variability. The aim of the study is to determine the impact of cellular electrophysiological variability on ectopic beats. Using a population of models approach to introduce regional and cellular variability into the atrial model, ectopic beats were initiated in two locations. Six ectopic beats were applied at a BCL of 130-160ms. The variable model was compared with an equivalent regional homogenous model. Using consistent tissue CV between models, in both the healthy and AF remodeled cases the average model total activation time was later than the variable model (a delay of 26ms and 14ms respectively). After matching activation times, repolarization was later in the average than the variable models. Latest APD90 in the AF remodeled cases were 268ms for the average and 256ms in the variable model. This resulted in a difference in propagation of the ectopic beat. In conclusion, cellular variability has a significant impact on both the depolarization and repolarization phases in the atria for the healthy and AF cases
mRNA expression levels in failing human hearts predict cellular electrophysiological remodelling: A population−based simulation study
No full textDifferences in mRNA expression levels have been observed in failing versus non-failing human hearts for several membrane channel proteins and accessory subunits. These differences may play a causal role in electrophysiological changes observed in human heart failure and atrial fibrillation, such as action potential (AP) prolongation, increased AP triangulation, decreased intracellular calcium transient (CaT) magnitude and decreased CaT triangulation. Our goal is to investigate whether the information contained in mRNA measurements can be used to predict cardiac electrophysiological remodeling in heart failure using computational modeling. Using mRNA data recently obtained from failing and non-failing human hearts, we construct failing and non-failing cell populations incorporating natural variability and up/down regulation of channel conductivities. Six biomarkers are calculated for each cell in each population, at cycle lengths between 1500 ms and 300 ms. Regression analysis is performed to determine which ion channels drive biomarker variability in failing versus non-failing cardiomyocytes. Our models suggest that reported mRNA expression changes are consistent with AP prolongation, increased AP triangulation, increased CaT duration, decreased CaT triangulation and amplitude, and increased delay between AP and CaT upstrokes in the failing population. Regression analysis reveals that changes in AP biomarkers are driven primarily by reduction in I, and changes in CaT biomarkers are driven predominantly by reduction in I and SERCA. In particular, the role of I is pacing rate dependent. Additionally, alternans developed at fast pacing rates for both failing and non-failing cardiomyocytes, but the underlying mechanisms are different in control and heart failure
Interactive effect of beta-adrenergic stimulation and mechanical stretch on low-frequency oscillations of ventricular action potential duration in humans
No full textVentricular repolarization dynamics are crucial to arrhythmogenesis. Low-frequency oscillations of repolarization have recently been reported in humans and the magnitude of these oscillations proposed to be a strong predictor of sudden cardiac death. Available evidence suggests a role of the sympathetic nervous system. We have used biophysically detailed models integrating ventricular electrophysiology, calcium dynamics, mechanics and β-adrenergic signaling to investigate the underlying mechanisms. The main results were: (1) Phasic beta-adrenergic stimulation (β-AS) at a Mayer wave frequency between 0.03 and 0.15Hz resulted in a gradual decrease of action potential (AP) duration (APD) with concomitant small APD oscillations. (2) After 3-4minutes of phasic β-AS, the mean APD adapted and oscillations of APD became apparent. (3) Phasic changes in haemodynamic loading at the same Mayer wave frequency (a known accompaniment of enhanced sympathetic nerve activity), simulated as variations in the sarcomere length, also induced APD oscillations. (4) The effect of phasic β-AS and haemodynamic loading on the magnitude of APD oscillations was synergistic. (5) The presence of calcium overload and reduced repolarization reserve further enhanced the magnitude of APD oscillations and was accompanied by afterdepolarizations and/or spontaneous APs. In conclusion, low-frequency oscillations of repolarization recently reported in humans were induced by phasic β-AS and phasic mechanical loading, which acted synergistically, and were greatly enhanced by disease-associated conditions, leading to arrhythmogenic events
Why Does Extracellular Potassium Rise in Acute Ischemia? Insights from Computational Simulations
No full text[EN] Hyperkalemia, acidosis and hypoxia are the three main
components of acute myocardial ischemia. In particular,
the increase of extracellular K+
concentration
(hyperkalemia), has been proved to be very proarrhythmic
because it sets the stage for ventricular fibrillation.
However, the intimate mechanisms remain partially
unknown. The aim of this work was to investigate, using
computational simulation, the relationship between the
different phases of hiperkalemia, the activity of the ion
channels and the changes related to the action potential in
the absence of coronary flow. Our results show that the
partial inhibition of the sodium-potassium pump is the
main cause of extracellular potassium accumulation.
However, the cause of the plateau phase could be due to
the appearance of action potential alternans, which
reduces the net potassium efflux and limits the increase of
extracellular potassium concentration.This work was partially supported by the "Programa
Salvador de Madariaga 2018" of the Spanish Ministry of
Science, Innovation and Universities (Grant Reference
PRX18/00489).González-Ascaso, A.; Olcina, P.; Garcia-Daras, M.; Rodriguez Matas, JF.; Ferrero De Loma-Osorio, JM. (2019). Why Does Extracellular Potassium Rise in Acute Ischemia? Insights from Computational Smilations. IEEE. 1-4. https://doi.org/10.22489/CinC.2019.088S1
Computational investigation of the role of low-density lipoprotein and oxygen transport in atherosclerotic arteries
No full textGeneration of a Virtual Cohort of Patients for in Silico Trials of Acute Ischemic Stroke Treatments
No full textThe development of in silico trials based on high-fidelity simulations of clinical procedures requires the availability of large cohorts of three-dimensional (3D) patient-specific anatomy models, which are often hard to collect due to limited availability and/or accessibility and imaging quality. Statistical shape modeling (SSM) allows one to identify the main modes of shape variation and to generate new samples based on the variability observed in a training dataset. In this work, a method for the automatic 3D reconstruction of vascular anatomies based on SSM is used for the generation of a virtual cohort of cerebrovascular models suitable for computational simulations, useful for in silico stroke trials. Starting from 88 cerebrovascular anatomies segmented from stroke patients’ images, an SSM algorithm was developed to generate a virtual population of 100 vascular anatomies, defined by centerlines and diameters. An acceptance criterion was defined based on geometric parameters, resulting in the acceptance of 83 generated anatomies. The 3D reconstruction method was validated by reconstructing a cerebrovascular phantom lumen and comparing the result with an STL geometry obtained from a computed tomography scan. In conclusion, the final 3D models of the generated anatomies show that the proposed methodology can produce a reliable cohort of cerebral arteries
