Abstract

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. Within the traditional time-varying elastance model, cardiac self-organization and breakdown cannot be addressed due to its inability to incorporate the dynamics of various feedback mechanisms consistently. To face this challenge, we recently proposed a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating mechanical, electric and chemical activity on micro-scale sarcomere and macro-scale heart. In this paper, by using our synergistic model, we investigate the mechano-electric feedback (MEF) which is the effect of mechanical activities on electric activity-one of the important feedback loops in cardiac function. We show that the (dysfunction of) MEF leads to various forms of heart arrhythmias, for instance, causing the electric activity and left-ventricular volume and pressure to oscillate too fast, too slowly, or erratically through periodic doubling bifurcations or ectopic excitations of incommensurable frequencies. This can result in a pathological condition, reminiscent of dilated cardiomyopathy, where a heart cannot contract or relax properly, with an ineffective cardiac pumping and abnormal electric activities. This pathological condition is then shown to be improved by a heart assist device (an axial rotary pump) since the latter tends to increase the stroke volume and aortic pressure while inhibiting the progression (bifurcation) to such a pathological condition. These results highlight a nontrivial effect of a mechanical pump on the electric activity of the heart.

Highlights

  • The human heart is a powerful yet complex organ and its failure is the leading cause of death worldwide

  • One of the important feedback loops in cardiac function is the effect of mechanical activities on electric activity—the so-called mechano-electric feedback (MEF) [4,5,6,7,8,9,10,11,12]

  • MEF is complementary to the electric-contraction coupling (ECC) where the electric activity causes the heart contraction and mechanical deformation

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Summary

Introduction

The human heart is a powerful yet complex organ and its failure is the leading cause of death worldwide. It constitutes one of the most beautiful examples of self-organization (homeostasis) [1,2,3] as a result of various control and feedback mechanisms across scales from micro-scale sarcomere to macro-scale organ levels. One of the important feedback loops in cardiac function is the effect of mechanical activities on electric activity—the so-called mechano-electric feedback (MEF) [4,5,6,7,8,9,10,11,12]. Systolic stretch reduces the amplitude of the action potential plateau [19] and shortens action potential duration or the early part of repolarisation depending on preparation and amplitude of stretch, potentially contributing to arrhythmias

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