An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system

B. Bhattacharya-Ghosh, S. Bozkurt, M.C.M. Rutten, F.N. Vosse, van de, V. Díaz-Zuccarini

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Abstract

Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.
Original languageEnglish
Pages (from-to)141-153
Number of pages13
JournalComputers in Biology and Medicine
Volume53
DOIs
Publication statusPublished - 2014

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Cardiovascular system
Dilated Cardiomyopathy
Cardiovascular System
Computer Simulation
Calcium
Heart Atria
Heart Ventricles
Proteins
Heart-Assist Devices
Calcium-Binding Proteins
Pulmonary Veins
Calcium Channels
Pulmonary Artery
Action Potentials
Left ventricular assist devices
Heart Failure
Pathology
Pressure
Therapeutics

Cite this

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abstract = "Mathematical modelling has been used to comprehend the pathology and the assessment of different treatment techniques such as heart failure and left ventricular assist device therapy in the cardiovascular field. In this study, an in-silico model of the heart is developed to understand the effects of idiopathic dilated cardiomyopathy (IDC) as a pathological scenario, with mechanisms described at the cellular, protein and organ levels. This model includes the right and left atria and ventricles, as well as the systemic and pulmonary arteries and veins. First, a multi-scale model of the whole heart is simulated for healthy conditions. Subsequently, the model is modified at its microscopic and macroscopic spatial scale to obtain the characteristics of IDC. The extracellular calcium concentration, the binding affinity of calcium binding proteins and the maximum and minimum elastances have been identified as key parameters across all relevant scales. The modified parameters cause a change in (a) intracellular calcium concentration characterising cellular properties, such as calcium channel currents or the action potential, (b) the proteins being involved in the sliding filament mechanism and the proportion of the attached crossbridges at the protein level, as well as (c) the pressure and volume values at the organ level. This model allows to obtain insight and understanding of the effects of the treatment techniques, from a physiological and biological point of view.",
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An in silico case study of idiopathic dilated cardiomyopathy via a multi-scale model of the cardiovascular system. / Bhattacharya-Ghosh, B.; Bozkurt, S.; Rutten, M.C.M.; Vosse, van de, F.N.; Díaz-Zuccarini, V.

In: Computers in Biology and Medicine, Vol. 53, 2014, p. 141-153.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Díaz-Zuccarini, V.

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