Activation sequence as a key factor in spatio-temporal optimization of myocardial function

Abstract

Using one-dimensional models of myocardial tissue, implemented as chains of virtual ventricular muscle segments that are kinematically connected in series, we studied the role of the excitation sequence in spatio-temporal organization of cardiac function. Each model element was represented by a well-verified mathematical model of cardiac electro-mechanical activity. We found that homogeneous chains, consisting of identical elements, respond to non-simultaneous stimulation by generation of complex spatio-temporal heterogeneities in element deformation. These are accompanied by the establishment of marked gradients in local electro-mechanical properties of the elements (heterogeneity in action potential duration, Ca2+ transient characteristics and sarcoplasmic reticulum Ca2+ loading). In heterogeneous chains, composed of elements simulating fast and slow contracting cardiomyocytes from different transmural layers, we found that only activation sequences where stimulation of the slower elements preceded that of faster ones gave rise to optimization of the system's electro-mechanical function, which was confirmed experimentally. Based on the results obtained, we hypothesize that the sequence of activation of cardiomyocytes in different ventricular layers is one of the key factors of spatio-temporal organization of myocardium. Moreover, activation sequence and regional differences in intrinsic electro-mechanical properties of cardiac muscle must be matched in order to optimize myocardial function.

The effect of repolarization duration on the indices of the pump function of the heart ventricles in animals with different types of activation of the myocardium under ectopic excitation of ventricles

“…Besides, relative to "slow" muscle Са 2+ transition to a faster virtual muscle has a rapid contraction and shorter duration of action potential. At the same time, pacing of the "fast" muscle reduces the contractility of the myocardium, but pacing of the "slow" onechanges insignificantly [30,[34][35][36]. Thus, we can assume that the electrical pacing of the ventricular area with longer ARIs does not change the contractility, while pacing of the ventricular area with shorter ARIs leads to the reduction of the pump function of the heart.…”

“…This mechanism involves the change in the duration of local repolarization and homeostasis of cardiomyocytes [30].…”

“…Mathematical models of heterogeneous myocardium [28,30] show that excitation wave goes from "fast" to "slow" virtual cardiac muscle [30,33]. Under the similar amplitude of contraction: the "fast" muscle reached peak force earlier and relaxed faster, than the "slow" one.…”

Heterogeneity of Viscoelastic Properties of Myocardial Muscle Fiber: Mathematical Model

“…It is an experimental approach to studying biomechanical and bioelectrical properties of heterogeneous system consisting of two different units [9]. By the muscle duplex method it obtained some important features of the contractile function of interacting segments in heterogeneous myocardium [10]- [12]. Though the experimental study of heterogeneous systems consists of greater number of units, it is an awkward task to date.…”

Функциональная Неднородность Возникающая В Результате Электрического И Механического Взаимодействия Между Кардиомиоцитами В Математической Модели Однородного Волокна

“…We have earlier created mathematical models to study the effects of electrical and mechanical interactions between myocardial tissue segments [23] including a muscle duplex approach and discrete chain models, where two or several cardiac muscle segments connected in-series or in-parallel interact mechanically with each other [23,24]. In the framework of these discrete models we showed that the time lag in electrical excitation of the segments actually intrinsic to the activation of various region of the heart wall resulted in gradual changes in their behavior producing functional heterogeneity of the myocardium system [17].…”