Biology subjects

Solovyova, O.

Publications and source records attributed to Solovyova, O..

3 recordsLinked to original sources

bioRxiv2019

A Population Modelling Approach to Studying Age-Related Effects on Excitation-Contraction Coupling in Human Cardiomyocytes

AO_SCPLOWBSTRACTC_SCPLOWAgeing is the dominant risk factor for cardiovascular diseases. A great body of experimental data has been gathered on cellular remodelling in the Ageing myocardium from animals. Very few experimental data are available on age-related changes in the human cardiomyocyte. We have used our combined electromechanical model of the human cardiomyocyte and the population modelling approach to investigate the variability in the response of cardiomyocytes to age-related changes in the model parameters. To generate the model population, we varied nine model parameters and excluded model samples with biomarkers falling outside of the physiological ranges. We evaluated the response to age-related changes in four electrophysiological model parameters reported in the literature: reduction in the density of the K+ transient outward current, maximal velocity of SERCA, and an increase in the density of NaCa exchange current and CaL-type current. The sensitivity of the action potential biomarkers to individual parameter variations was assessed. Each parameter modulation caused an increase in APD, while the sensitivity of the model to changes in GCaL and Vmax_up was much higher than to those in the effects of Gto and KNaCa. Then 60 age-related sets of the four parameters were randomly generated and each set was applied to every model in the control population. We calculated the frequency of model samples with repolarisation anomalies (RA) and the shortening of the electro-mechanical window in the ageing model populations as an arrhythmogenic ageing score. The linear dependence of the score on the deviation of the parameters showed a high determination coefficient with the most significant impact due to the age-related change in the CaL current. The population-based approach allowed us to classify models with low and high risk of age-related RA and to predict risks based on the control biomarkers.

physiology↗

bioRxiv2019

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ten Tusscher - Panfilov electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the Ekaterinburg - Oxford model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.

biophysics↗

bioRxiv2019

Model order reduction for left ventricular mechanics via congruency training

Computational models of the cardiovascular system and heart function are currently being investigated as analytic tools to assist medical practice and clinical trials. Recent technological advances allow for finite element models of heart ventricles and atria to be customized to medical images and to assimilate electrical and hemodynamic measurements. Optimizing model parameters to physiological data is, however, challenging due to the computational complexity of finite element models. Metaheuristic algorithms and other optimization strategies typically require sampling hundreds of points in the model parameter space before converging to optimal solutions. Similarly, resolving uncertainty of model outputs to input assumptions is difficult for finite element models due to their computational cost. In this paper, we present a novel, multifidelity strategy for model order reduction of 3-D finite element models of ventricular mechanics. Our approach is centered around well established findings on the similarity between contraction of an isolated muscle and the whole ventricle. Specifically, we demonstrate that simple linear transformations between sarcomere strain (tension) and ventricular volume (pressure) are sufficient to reproduce global pressure-volume outputs of 3-D finite element models even by a reduced model with just a single myocyte unit. We further develop a procedure for congruency training of a surrogate low-order model from multi-scale finite elements, and we construct an example of parameter optimization based on medical images. We discuss how the presented approach might be employed to process large datasets of medical images as well as databases of echocardiographic reports, paving the way towards application of heart mechanics models in the clinical practice.

biophysics↗