Mechano-electrical feedback in the clinical setting: Current perspectives

Orini, Michele; Nanda, Akriti; Yates, Martin T.; Salvo, Carmelo Di; Roberts, Neil; Lambiase, Pier D.; Taggart, Peter

doi:10.1016/j.pbiomolbio.2017.06.001

Cited by 30 publications

(36 citation statements)

References 152 publications

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g., load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the 'ten Tusscher-Panfilov' electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the 'Ekaterinburg-Oxford' model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.

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Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…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].…”

mentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

“…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].…”

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

Balakina-Vikulova

Panfilov

Solovyova

et al. 2019

Preprint

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Experiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. In in vitro experiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart muscle in vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ‘ten Tusscher – Panfilov’ electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the ‘Ekaterinburg – Oxford’ model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.

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Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval

Ramírez

Duijvenboden

Young

et al. 2020

The American Journal of Human Genetics

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Sudden cardiac death is responsible for half of all deaths from cardiovascular disease. The analysis of the electrophysiological substrate for arrhythmias is crucial for optimal risk stratification. A prolonged T-peak-to-Tend (Tpe) interval on the electrocardiogram is an independent predictor of increased arrhythmic risk, and Tpe changes with heart rate are even stronger predictors. However, our understanding of the electrophysiological mechanisms supporting these risk factors is limited. We conducted genome-wide association studies (GWASs) for resting Tpe and Tpe response to exercise and recovery in $30,000 individuals, followed by replication in independent samples ($42,000 for resting Tpe and $22,000 for Tpe response to exercise and recovery), all from UK Biobank. Fifteen and one single-nucleotide variants for resting Tpe and Tpe response to exercise, respectively, were formally replicated. In a full dataset GWAS, 13 further loci for resting Tpe, 1 for Tpe response to exercise and 1 for Tpe response to exercise were genome-wide significant (p % 5 3 10 À8 ). Sex-specific analyses indicated seven additional loci. In total, we identify 32 loci for resting Tpe, 3 for Tpe response to exercise and 3 for Tpe response to recovery modulating ventricular repolarization, as well as cardiac conduction and contraction. Our findings shed light on the genetic basis of resting Tpe and Tpe response to exercise and recovery, unveiling plausible candidate genes and biological mechanisms underlying ventricular excitability.

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Mechano-electrical feedback in the clinical setting: Current perspectives

Cited by 30 publications

References 152 publications

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

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

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

Common Genetic Variants Modulate the Electrocardiographic Tpeak-to-Tend Interval

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