Bhattacharya-Ghosh Benjamin, Bozkurt Selim, Rutten Marcel C M, van de Vosse Frans N, Díaz-Zuccarini Vanessa
University College London, Mechanical Engineering Department, Torrington Place, WC1E 7JE London, UK.
Eindhoven University of Technology, Biomedical Engineering, Materials Technology, PO Box 513, GEM-Z 4.18, 5600 MB, Eindhoven, The Netherlands.
Comput Biol Med. 2014 Oct;53:141-53. doi: 10.1016/j.compbiomed.2014.06.013. Epub 2014 Jul 6.
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.
数学建模已被用于理解心血管领域中不同治疗技术（如心力衰竭和左心室辅助装置治疗）的病理情况和评估。在本研究中，开发了一种心脏的计算机模型，以了解特发性扩张型心肌病（IDC）作为一种病理情况的影响，并在细胞、蛋白质和器官水平描述其机制。该模型包括右心房和左心房、右心室和左心室，以及体循环和肺循环的动脉和静脉。首先，针对健康状况模拟了整个心脏的多尺度模型。随后，在微观和宏观空间尺度上对模型进行修改，以获得IDC的特征。细胞外钙浓度、钙结合蛋白的结合亲和力以及最大和最小弹性已被确定为所有相关尺度上的关键参数。修改后的参数导致（a）表征细胞特性（如钙通道电流或动作电位）的细胞内钙浓度发生变化，（b）参与肌丝滑动机制的蛋白质以及蛋白质水平上附着的横桥比例发生变化，以及（c）器官水平上的压力和体积值发生变化。该模型有助于从生理和生物学角度深入了解和理解治疗技术的效果。
