Mechano-electrical feedback in the clinical setting: Current perspectives

Abstract

Mechano-electric feedback (MEF) is an established mechanism whereby myocardial deformation causes changes in cardiac electrophysiological parameters. Extensive animal, laboratory and theoretical investigation has demonstrated that abnormal patterns of cardiac strain can induce alteration of electrical excitation and recovery through MEF, which can potentially contribute to the establishment of dangerous arrhythmias. However, the clinical relevance of MEF in patients with heart disease remains to be established. This paper reviews up-to date experimental evidence describing the response to different types of mechanical stimuli in the intact human heart with the support of new data collected during cardiac surgery. It discusses modulatory effects of MEF that may contribute to increase the vulnerability to arrhythmia and describes MEF interaction with clinical conditions where mechanically induced changes in cardiac electrophysiology are likely to be more relevant. Finally, directions for future studies, including the need for in-vivo human data providing simultaneous assessment of the distribution of structural, functional and electrophysiological parameters at the regional level, are identified.

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

“…We have shown that MCF and MEF both for smaller afterloads as compared to bigger ones and for various mechanical interventions during isometric and isotonic twitches substantially affect durations of calcium transient and action potential in the human cardiomyocyte model. Although the main function of electrical excitation in the heart is to initiate mechanical contraction, mechanical contraction also affects electrical wave propagation via processes called mechano-calcium feedbacks (MCF) and mechano-electric feedbacks (MEF) [1][2][3]. Physiological role of the influence of mechanical conditions on the activity of the heart muscle is manifested, in particular, in adaptation of normal myocardium to varying external and internal mechanical conditions of contraction, including global and local mechanical loading and length redistribution between interacting heterogeneous cardiomyocytes in the heart chamber walls [4].…”

“…On the other hand, the pathological manifestations of these feedbacks can be quite dramatic: for example, they can cause heart rhythm disturbances and even lead to sudden cardiac death [1]. The experimental data on the electromechanical activity are mainly collected in animal heart; however, data for the human cardiomyocyte are very limited.…”

“…the MCF and MEF were revealed as the following basic classic phenomena: length dependence of isometric twitches, load dependence of isotonic contractions, muscle inactivation due to short-time deformations during isometric twitches (see [15] for a review), and in the respective responses of calcium transients and action potentials on the mechanical interventions. Such integrative data were purely reported for the human cardiac preparations, while plural clinical evidence for contraction-excitation feedback in humans, mechano-dependent arrhythmias included is published [1,16,17].…”

Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model

“…Although the main function of electrical excitation in the heart is to trigger mechanical contraction, the latter influences in turn electrical wave propagation via processes called mechano-calcium feedbacks (MCF) and mechano-electric feedbacks (MEF) [1][2][3]. Physiologically, mechanical conditions ensure the adaptation of the normal myocardium to varying external and internal mechanical conditions of contraction, including global and local mechanical loading and length Page 2 of 23 Balakina- Vikulova et al J Physiol Sci (2020) 70:12 duplexes, and one-dimensional models of heterogeneous cardiac tissue [5,6,[8][9][10].…”

“…On the other hand, the pathological manifestations of these feedbacks can be quite dramatic: for example, they can cause heart rhythm disturbances and even lead to sudden cardiac death [1]. Experimental data on electromechanical activity are available mostly for animal hearts, while data for the human cardiomyocyte are very limited.…”