Model of Anisotropic Reverse Cardiac Growth in Mechanical Dyssynchrony

Jayavel Arumugam,Lik Chuan Lee,Joy Mojumder,Ghassan Kassab

doi:10.1038/s41598-019-48670-8

Jayavel Arumugam, Lik Chuan Lee + Show 2 more

Open Access

https://doi.org/10.1038/s41598-019-48670-8

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Abstract

Based on recent single-cell experiments showing that longitudinal myocyte stretch produces both parallel and serial addition of sarcomeres, we developed an anisotropic growth constitutive model with elastic myofiber stretch as the growth stimuli to simulate long-term changes in biventricular geometry associated with alterations in cardiac electromechanics. The constitutive model is developed based on the volumetric growth framework. In the model, local growth evolutions of the myocyte’s longitudinal and transverse directions are driven by the deviations of maximum elastic myofiber stretch over a cardiac cycle from its corresponding local homeostatic set point, but with different sensitivities. Local homeostatic set point is determined from a simulation with normal activation pattern. The growth constitutive model is coupled to an electromechanics model and calibrated based on both global and local ventricular geometrical changes associated with chronic left ventricular free wall pacing found in previous animal experiments. We show that the coupled electromechanics-growth model can quantitatively reproduce the following: (1) Thinning and thickening of the ventricular wall respectively at early and late activated regions and (2) Global left ventricular dilation as measured in experiments. These findings reinforce the role of elastic myofiber stretch as a growth stimulant at both cellular level and tissue-level.

Highlights

Computational modeling is increasingly used to simulate long-term changes associated with cardiac growth
We show that with appropriate calibration of the growth rates, the coupled electromechanics-growth model can reproduce changes in the biventricular geometry that are qualitatively comparable with previous experimental measurements and clinical observations[5,17], suggesting that it is possible for myofiber stretch to be the sole growth stimulant in mechanical dyssynchrony
Motivated by a recent experiment showing that longitudinal stretching of myocyte produces both longitudinal and transverse growth via parallel and serial sarcomeric addition[15], we have presented an anisotropic growth and remodeling (G&R) constitutive model in which the changes in lengths of the tissue in 3 orthogonal material directions are driven locally by the deviation of maximum elastic myofiber stretch from its corresponding homeostatic set point value

Summary

Introduction

Computational modeling is increasingly used to simulate long-term changes associated with cardiac growth. Formulated based on the volumetric growth framework in which the deformation gradient tensor is multiplicatively decomposed into an elastic and a growth component[6,7], cardiac growth constitutive models are developed to phenomenologically describe local changes in shape and size of the myocytes in response to local alterations of cardiac mechanics (i.e., stresses) and/or kinematics (i.e., strains) These constitutive models are usually coupled with a computational cardiac mechanics model to simulate the collective geometrical changes of the myocytes associated with alterations in loading conditions[8,9,10,11] in a realistic ventricular geometry. Motivated by these experimental observations, we seek here to investigate if prescribing myofiber stretch as a single stimulus that controls growth in the myofiber and transverse directions (with different sensitivity) can quantitatively reproduce long term changes in ventricular geometry associated with mechanical dyssynchrony. We show that with appropriate calibration of the growth rates, the coupled electromechanics-growth model can reproduce changes in the biventricular geometry that are qualitatively comparable with previous experimental measurements and clinical observations[5,17], suggesting that it is possible for myofiber stretch to be the sole growth stimulant in mechanical dyssynchrony

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