Hemodynamic effects of alpha-tropomyosin mutations associated with inherited cardiomyopathies: Multiscale simulation

The effects of two cardiomyopathy-associated mutations in regulatory sarcomere protein tropomyosin (Tpm) on heart function were studied with a new multiscale model of the cardiovascular system (CVS). They were a Tpm mutation, Ile284Val, associated with hypertrophic cardiomyopathy (HCM), and an Asp230Asn one associated with dilated cardiomyopathy (DCM). When the molecular and cell-level changes in the Ca2+ regulation of cardiac muscle caused by these mutations were introduced into the myocardial model of the left ventricle (LV) while the LV shape remained the same as in the model of the normal heart, the cardiac output and arterial blood pressure reduced. Simulations of LV hypertrophy in the case of the Ile284Val mutation and LV dilatation in the case of the Asp230Asn mutation demonstrated that the LV remodeling partially recovered the stroke volume and arterial blood pressure, confirming that both hypertrophy and dilatation help to preserve the LV function. The possible effects of changes in passive myocardial stiffness in the model according to data reported for HCM and DCM hearts were also simulated. The results of the simulations showed that the end-systolic pressure-volume relation that is often used to characterize heart contractility strongly depends on heart geometry and cannot be used as a characteristic of myocardial contractility. © 2020 by the authors.

Authors
Syomin F. 1, 2 , Khabibullina A.3 , Osepyan A.1, 3 , Tsaturyan A.1
Journal
Publisher
MDPI AG
Number of issue
7
Language
English
Status
Published
Number
1169
Volume
8
Year
2020
Organizations
  • 1 Institute of Mechanics, Lomonosov Moscow State University, Moscow, 119192, Russian Federation
  • 2 Peoples' Friendship University of Russia (RUDN University), Moscow, 117198, Russian Federation
  • 3 Mathematics and Mechanics Department, Lomonosov Moscow State University, Moscow, 119991, Russian Federation
Keywords
Cardiac mechanics; Cardiomyopathies; Left ventricle remodeling; Mathematical modeling; Multiscale simulation
Date of creation
02.11.2020
Date of change
02.11.2020
Short link
https://repository.rudn.ru/en/records/article/record/64561/
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