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

Tópicos

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Resumo

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.

Resumo Limpo

mathemat model use comprehend patholog assess differ treatment techniqu heart failur left ventricular assist devic therapi cardiovascular field studi insilico model heart develop understand effect idiopath dilat cardiomyopathi idc patholog scenario mechan describ cellular protein organ level model includ right left atria ventricl well system pulmonari arteri vein first multiscal model whole heart simul healthi condit subsequ model modifi microscop macroscop spatial scale obtain characterist idc extracellular calcium concentr bind affin calcium bind protein maximum minimum elast identifi key paramet across relev scale modifi paramet caus chang intracellular calcium concentr characteris cellular properti calcium channel current action potenti b protein involv slide filament mechan proport attach crossbridg protein level well c pressur volum valu organ level model allow obtain insight understand effect treatment techniqu physiolog biolog point view

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